Journal Description
Immuno
Immuno
is an international, peer-reviewed, open access journal on immunological research and clinical applications published quarterly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within ESCI (Web of Science), Scopus, EBSCO, and other databases.
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 26.8 days after submission; acceptance to publication is undertaken in 2.2 days (median values for papers published in this journal in the second half of 2024).
- Journal Rank: CiteScore - Q2 (Medicine (miscellaneous))
- Recognition of Reviewers: APC discount vouchers, optional signed peer review, and reviewer names published annually in the journal.
Impact Factor:
2.1 (2023);
5-Year Impact Factor:
2.1 (2023)
Latest Articles
Impact of Sympathetic Nervous System Activation and Inflammatory Response on Periodontitis Severity
Immuno 2025, 5(2), 22; https://doi.org/10.3390/immuno5020022 - 5 Jun 2025
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The sympathetic nervous system (SNS) is crucial for stress response regulation and immune modulation. Prolonged SNS activation, often induced by stress exposure, disrupts immune homeostasis and intensifies inflammatory processes, contributing to periodontal disease progression. This study investigates the relationship between SNS activity and
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The sympathetic nervous system (SNS) is crucial for stress response regulation and immune modulation. Prolonged SNS activation, often induced by stress exposure, disrupts immune homeostasis and intensifies inflammatory processes, contributing to periodontal disease progression. This study investigates the relationship between SNS activity and periodontitis severity, utilizing salivary biomarkers chromogranin A (CgA) and alpha-amylase (sAA) alongside pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-6 (IL-6). Saliva samples from 67 patients, categorized by periodontitis severity (Stages I/II and III/IV), were analyzed using enzyme-linked immunosorbent assay (ELISA). The results revealed significantly higher median levels of CgA (9.45 vs. 3.93 pmol/mL) and IL-1β (257.81 vs. 220.11 pg/mL) in patients with Stage III/IV periodontitis compared with those with Stage I/II, indicating heightened SNS activity and inflammatory response. Correlations between these biomarkers and clinical periodontal parameters, such as probing depth and clinical attachment loss, further support these findings. Despite elevated sAA levels in severe cases, statistical significance was not achieved. IL-6 levels also showed no significant variation across disease stages, although trends aligned with increased severity. This study highlights the interplay between SNA activation and periodontal inflammation, as evidenced by elevated salivary levels of CgA and IL-1β in patients with advanced periodontitis. By integrating neuroendocrine and inflammatory biomarkers into the diagnostic process, clinicians may be able to better identify patients at increased risk for periodontal breakdown and to consider adjunctive interventions such as stress management, thereby supporting more personalized approaches to periodontitis treatment.
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Open AccessArticle
Complete Blood Count-Derived Biomarkers’ Association with Risk of PD-1 or PD-1/CTLA-4 Inhibitor-Induced Hypothyroidism in Patients with Solid Tumors
by
Ketevan Lomidze, Nino Kikodze, Marine Gordeladze, Nino Charkviani and Tinatin Chikovani
Immuno 2025, 5(2), 21; https://doi.org/10.3390/immuno5020021 - 4 Jun 2025
Abstract
Background: A novel and highly effective strategy for tumor immunotherapy involves enhancing host immune responses against tumors through the blockade of checkpoint molecules. The most common toxicities associated with checkpoint blockade therapies include autoimmune damage to various organs. Purpose: This study aims to
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Background: A novel and highly effective strategy for tumor immunotherapy involves enhancing host immune responses against tumors through the blockade of checkpoint molecules. The most common toxicities associated with checkpoint blockade therapies include autoimmune damage to various organs. Purpose: This study aims to investigate hematological markers derived from complete blood counts (CBCs)—including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), derived neutrophil-to-lymphocyte ratio (dNLR), white blood cell-to-hemoglobin ratio (WHR), neutrophils, lymphocytes, platelets, hemoglobin, red blood cell (RBC) count, neutrophil-to-RBC ratio (NRR), and neutrophil-to-hemoglobin ratio (NHR)—as potential prognostic biomarkers for the early identification of hypothyroidism in patients receiving PD-1 or PD-1/CTLA-4 immune checkpoint inhibitors. Materials and Methods: A prospective observational study was conducted on 44 patients with stage III-IV solid tumors treated with immune checkpoint (PD-1 or PD-1/CTLA-4) inhibitors. Thyroid function tests and CBC-derived biomarkers were collected at baseline, before immunotherapy. In the immunotherapy cohort, 15 of the 44 patients developed immune-related hypothyroidism, defined as overt autoimmune thyroiditis (TSH > 4.0, FT4 < 12, and anti-TPO antibodies > 30 IU/mL and/or anti-TG antibodies > 95 IU/mL) (Group 1). In comparison, 29 patients maintained normal thyroid function (Group 2). The control group comprised 14 age- and sex-matched healthy volunteers (Group 3). Statistical analyses were performed using analysis of variance (ANOVA) to compare blood parameters among the three groups (Group 1, Group 2, and Group 3) before treatment, with statistical significance set at a p-value < 0.05. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic power of the potential prognostic biomarkers areas. The area under the curve (AUC), sensitivity, and specificity were calculated for the 44 immunotherapy patients. Results: The PLR was significantly higher (262.25 ± 162.95), while WBCs-neutrophils, the WHR, the NRR, the NHR, WBCs, neutrophils, and lymphocytes were lower (2.07 ± 0.66, 0.54 ± 0.19, 0.96 ± 0.28, 0.36 ± 0.14, 6.36 ± 2.07, 4.29 ± 1.55, and 1.23 ± 0.41, respectively) at baseline in Group 1 in comparison to Group 2. ROC curve analysis revealed that the areas under the curve (AUC) for WBCs, neutrophils, lymphocytes, WBCs-neutrophils, the PLR, the WHR, the NRR, and the NHR were 0.9, 0.87, 0.83, 0.85, 0.84, 0.92, 0.89, and 0.87, respectively. These values exceeded the threshold, indicating the high prognostic potential of each marker. Conclusions: Lower baseline levels of WBCs-neutrophils, the WHR, the NRR, the NHR, WBCs, neutrophils, and lymphocytes, along with a higher PLR, were associated with an increased risk of hypothyroidism in patients receiving PD-1 or PD-1/CTLA-4 inhibitors. These CBC-derived biomarkers represent simple, accessible, and potentially useful tools for predicting hypothyroidism in cancer patients undergoing immunotherapy. Further studies in bigger cohorts are needed to validate our findings.
Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
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Open AccessReview
Relevance of Antibody-Dependent Enhancement in COVID-19
by
Daniel Rodriguez-Pinto and María Sol Mendoza-Ruiz
Immuno 2025, 5(2), 20; https://doi.org/10.3390/immuno5020020 - 2 Jun 2025
Abstract
Antibody-dependent enhancement (ADE) is a well-established mechanism of pathology in several viral diseases, but its relevance in COVID-19 is not yet recognized. Although several studies in humans have shown an association between antibody responses and disease severity, long term studies addressing the presence
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Antibody-dependent enhancement (ADE) is a well-established mechanism of pathology in several viral diseases, but its relevance in COVID-19 is not yet recognized. Although several studies in humans have shown an association between antibody responses and disease severity, long term studies addressing the presence of antibodies before infection and their neutralization capacity are needed to establish ADE. Mechanistic studies have determined that the entry of SARS-CoV-2 into host cells can be mediated by immune complexes through Fcγ receptors or by favoring ACE2 conformation. However, the impact on viral replication is not clear. There is evidence for enhancing effects of immune complexes on Fcγ receptor-mediated effector mechanisms and cytokine secretion after modulation of cell signaling in immune cells, specially by antibodies with altered glycosylation, which points to ADE that can contribute to COVID-19 pathology. However, more studies are needed to determine the impact of antibodies both in naturally infected and vaccinated subjects, which can lead to their use as a prognostic marker and increase vaccine safety.
Full article
(This article belongs to the Section Infectious Immunology and Vaccines)
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Open AccessReview
Immunomodulatory and Anti-Inflammatory Properties of Honey and Bee Products
by
Bashar Saad
Immuno 2025, 5(2), 19; https://doi.org/10.3390/immuno5020019 - 30 May 2025
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Honey and other bee products, including propolis, royal jelly, and bee pollen, are widely recognized for their medicinal properties. Among their numerous biological activities, their anti-inflammatory and immunomodulatory effects have gained significant attention in recent years. Immune and inflammatory disorders contribute significantly to
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Honey and other bee products, including propolis, royal jelly, and bee pollen, are widely recognized for their medicinal properties. Among their numerous biological activities, their anti-inflammatory and immunomodulatory effects have gained significant attention in recent years. Immune and inflammatory disorders contribute significantly to the development of chronic conditions, including cancer and diabetes. Bee-derived products, along with their bioactive compounds such as polyphenols, have shown promising therapeutic effects in modulating inflammatory mediators. Studies indicate that these products help regulate tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), and interleukin-7 (IL-7) levels while reducing reactive oxygen species (ROS) production. Additionally, both in vitro and in vivo research, along with clinical studies, highlight their role in enhancing immune responses by activating B and T lymphocytes. This review explores the molecular mechanisms underlying these properties, emphasizing the role of bioactive compounds such as flavonoids, phenolic acids, and proteins in modulating immune responses and reducing inflammation. Evidence from in vitro, in vivo, and clinical studies suggests that honey and bee products influence cytokine production, regulate immune cell activity, and mitigate oxidative stress, making them potential therapeutic agents for inflammatory and immune-related disorders. To gather relevant information, databases such as Google Scholar, PubMed, and ScienceDirect were searched using various keyword combinations, including immunomodulatory, anti-inflammatory, bee products, honey, propolis, royal jelly, bee venom, and bee pollen. Given their anti-inflammatory, immune-protective, antioxidant, anti-apoptotic, and antimicrobial properties, bee products remain a subject of interest for further clinical evaluation.
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Open AccessReview
Efficacy of Intravenous Immunoglobulins and Other Immunotherapies in Neurological Disorders and Immunological Mechanisms Involved
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Angel Justiz-Vaillant, Sachin Soodeen, Odalis Asin-Milan, Julio Morales-Esquivel and Rodolfo Arozarena-Fundora
Immuno 2025, 5(2), 18; https://doi.org/10.3390/immuno5020018 - 26 May 2025
Abstract
This review aims to explore the role of immunotherapeutic strategies—primarily intravenous immunoglobulin (IVIG), plasma exchange (PLEX), and selected immunomodulatory agents—in the treatment of neurological and psychiatric disorders with suspected or confirmed autoimmune mechanisms. A central focus is placed on understanding the immunopathology of
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This review aims to explore the role of immunotherapeutic strategies—primarily intravenous immunoglobulin (IVIG), plasma exchange (PLEX), and selected immunomodulatory agents—in the treatment of neurological and psychiatric disorders with suspected or confirmed autoimmune mechanisms. A central focus is placed on understanding the immunopathology of these conditions through the identification and characterization of disease-associated autoantibodies. Disorders such as autoimmune encephalitis, myasthenia gravis, limbic epilepsy, neuropsychiatric systemic lupus erythematosus (NPSLE), and certain forms of schizophrenia have shown clinical responses to immunotherapy, suggesting an underlying autoimmune basis in a subset of patients. The review also highlights the diagnostic relevance of detecting autoantibodies targeting neuronal receptors, such as NMDA and AMPA receptors, or neuromuscular junction components, as biomarkers that guide therapeutic decisions. Furthermore, we synthesize findings from published randomized controlled trials (RCTs) that have validated the efficacy of IVIG and PLEX in specific diseases, such as Guillain–Barré syndrome, and myasthenia gravis. Emerging clinical evidence supports expanding these treatments to other conditions where autoimmunity is implicated. By integrating immunological insights with clinical trial data, this review offers a comprehensive perspective on how immunotherapies may be tailored to target autoimmune contributors to neuropsychiatric disease.
Full article
(This article belongs to the Special Issue Nano-Pharmacology: Nanotechnology Based Therapeutics for Targeting Neuroinflammation)
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Open AccessBrief Report
Recurrent SARS-CoV-2 Infection Is Linked to the TLR7 rs179008 Variant and Related to Diminished Baseline T Cell Immunity
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Camilla Natália Oliveira Santos, Priscila Lima dos Santos, Angela Maria da Silva and Lucas Sousa Magalhães
Immuno 2025, 5(2), 17; https://doi.org/10.3390/immuno5020017 - 16 May 2025
Abstract
Recurrent COVID-19, defined as two or more distinct episodes, may reflect an impaired immune response to SARS-CoV-2. In this case–control study, we compared three groups: individuals with recurrent COVID-19, those with a single episode, and SARS-CoV-2-naïve controls. We genotyped six immune-related SNPs, including
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Recurrent COVID-19, defined as two or more distinct episodes, may reflect an impaired immune response to SARS-CoV-2. In this case–control study, we compared three groups: individuals with recurrent COVID-19, those with a single episode, and SARS-CoV-2-naïve controls. We genotyped six immune-related SNPs, including TLR7 rs179008, and measured CD4+ and CD8+ T cell responses to SARS-CoV-2 antigens using flow cytometry. The T allele of TLR7 rs179008, previously linked to reduced receptor expression, was significantly overrepresented in the recurrent COVID-19 cohort. At baseline, frequencies of IFN-γ+, IL-2+, and TNF-α+ cells among CD4+ and CD8+ T cells did not differ between groups. However, stratification by the rs179008 genotype revealed that T allele carriers displayed diminished IFN-γ production in both CD4+ and CD8+ T cells and reduced IL-2 production in CD4+ T cells. Following vaccination, T cell responses were comparable across all genotypes. The T allele of TLR7 rs179008 is associated with recurrent COVID-19 and may contribute to impaired T cell-mediated immunity. Further studies are warranted to elucidate the mechanistic role of TLR7 variation in SARS-CoV-2 reinfection risk.
Full article
(This article belongs to the Section Infectious Immunology and Vaccines)
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Open AccessArticle
Pre- and Post-Transplant Anti-BKV IgG Responses and HLA Associations in BK Virus Reactivation Among Renal Transplant Recipients
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Deema Ibrahim Fallatah and Steve Christmas
Immuno 2025, 5(2), 16; https://doi.org/10.3390/immuno5020016 - 9 May 2025
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BK virus (BKV) reactivation is a significant complication in renal transplant recipients, often leading to BK viremia and BK virus-associated nephropathy (BKVAN), which can compromise graft survival. While the routine monitoring of BKV DNA in blood aids in early detection, identifying pre-transplant risk
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BK virus (BKV) reactivation is a significant complication in renal transplant recipients, often leading to BK viremia and BK virus-associated nephropathy (BKVAN), which can compromise graft survival. While the routine monitoring of BKV DNA in blood aids in early detection, identifying pre-transplant risk factors remains a challenge. This study investigates the role of pre- and post-transplant anti-BKV IgG levels and human leukocyte antigen (HLA) alleles in predicting BKV reactivation. The hospital-based cross-sectional study was conducted on 38 renal transplant recipients, stratified into viremic, non-viremic, and BKVAN groups. Anti-BKV IgG levels were measured pre-transplant, at viremia onset, and post-viremia using ELISA. BKV DNA was detected via qPCR, and HLA typing was performed using sequence-specific oligonucleotide probe (SSOP) hybridization. Statistical analyses included Kaplan–Meier survival curves and Cox regression models. Pre-transplant anti-BKV IgG seropositivity was higher in viremic (94%) and BKVAN (100%) patients than in non-viremic recipients (66.6%). Post-transplant IgG levels increased significantly in viremic recipients (p < 0.05). HLA-B44 and HLA-DR15 were significantly associated with increased BKV viremia risk (p = 0.02 and p = 0.01, respectively). Pre-transplant anti-BKV IgG levels and specific HLA alleles influence BKV reactivation risk. These findings highlight the potential for integrating serological and genetic screening into pre-transplant assessments to improve risk stratification and post-transplant monitoring strategies.
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Open AccessArticle
Indole-3-Carbinol Enhances Alternative Activation of Macrophages via AHR Pathway and Glucose Transporter Regulation
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Delara Omrani, Saeed Mohammadi, Moein Malekzadeh, Mohsen Saeidi, Fakhri Sadat Seyedhosseini, Ahmed Al-Harrasi and Yaghoub Yazdani
Immuno 2025, 5(2), 15; https://doi.org/10.3390/immuno5020015 - 2 May 2025
Abstract
Disruption in macrophage polarization is linked to inflammatory diseases and metabolic disorders. Our study aimed to investigate how AHR activation by I3C and TCDD could impact glucose transporters and macrophage phenotypes and functions in human macrophages. Human monocyte-derived macrophages (hMDMs) and THP-1 cell-derived
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Disruption in macrophage polarization is linked to inflammatory diseases and metabolic disorders. Our study aimed to investigate how AHR activation by I3C and TCDD could impact glucose transporters and macrophage phenotypes and functions in human macrophages. Human monocyte-derived macrophages (hMDMs) and THP-1 cell-derived macrophage-like cells were treated for 24 h with 100 ng/mL LPS, 100 nM TCDD, and 10 ng/µL I3C. CYP1A1 and CYP1B1 expression was significantly increased in the I3C and TCDD treatments, with CYP1B1 showing a higher fold change in I3C compared to TCDD. The AHRR expression was the highest in the TCDD group. For macrophage polarization, I3C significantly elevated CD163 expression while reducing CD16 and CD86, indicative of M2-like polarization. Additionally, I3C promoted ARG1 expression and reduced NOS2 levels, while TCDD increased NOS2. A cytokine analysis revealed I3C-induced upregulation of IL-10 and TGF-β, while TCDD significantly elevated TNF-α and IL-12. I3C upregulated glucose transporter genes (GLUT1, GLUT3, GLUT6), in contrast to the downregulation observed in TCDD-treated cells. Our findings demonstrated that I3C distinctly modulates AHR activation genes, macrophage polarization, cytokine expression, and glucose transporter levels in THP-1 cells compared to the TCDD and LPS treatments. Our findings suggest that I3C favors an anti-inflammatory M2-like macrophage polarization coupled with enhanced metabolic activity.
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(This article belongs to the Section Innate Immunity and Inflammation)
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Open AccessSystematic Review
Turner Syndrome Increases the Risk of Psoriasis: A Systematic Review and Meta-Analysis
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Jirat Chenbhanich, Ben Ponvilawan and Patompong Ungprasert
Immuno 2025, 5(2), 14; https://doi.org/10.3390/immuno5020014 - 17 Apr 2025
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Aims: Patients with Turner syndrome (TS) may have a higher risk of psoriasis as suggested by some reports. Data on this association are still limited. We investigated the association between TS and the risk of prevalent and incident psoriasis by combining results from
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Aims: Patients with Turner syndrome (TS) may have a higher risk of psoriasis as suggested by some reports. Data on this association are still limited. We investigated the association between TS and the risk of prevalent and incident psoriasis by combining results from available studies using systematic reviews and meta-analysis techniques. Methods: Potentially eligible studies were identified from Medline and EMBASE databases from inception to December 2023 using a search strategy that comprised of terms for “Turner syndrome” and “psoriasis”. An eligible cohort study must comprise of two groups of participants—those with and without TS. It must report our outcome of interest—incidence and/or prevalence of psoriasis in each group. The pooled effect estimates were generated using the generic inverse variance method, which assigns weight to each study in reversal to its variance. Meta-analyses of the prevalent and incident psoriasis were conducted separately. Results: A total of 4919 articles were retrieved. After two rounds of independent review by two investigators, five cohort studies (two incident studies and three prevalent studies) met the eligibility criteria and were included in the meta-analyses. The meta-analyses found a significantly elevated risk of both incident and prevalent psoriasis in patients with TS compared to individuals without TS, with the pooled risk ratio of 5.58 (95% CI, 3.73–8.35; I2 0%) and 5.66 (95% CI, 1.52–21.03; I2 19%), respectively. Conclusions: An increased risk of both incident and prevalent psoriasis among patients with TS was demonstrated in this study.
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Open AccessReview
Role of Inflammatory Mediators in Chronic Obstructive Pulmonary Disease Pathogenesis: Updates and Perspectives
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Pankush, Khushboo Bharti, Rohit Pandey, Namita Srivastava, Shashank Kashyap, Deepak Kumar, Lokender Kumar, Sunil K. Suman and Sanjay K. S. Patel
Immuno 2025, 5(2), 13; https://doi.org/10.3390/immuno5020013 - 15 Apr 2025
Abstract
Chronic obstructive pulmonary disease (COPD) is a chronic, debilitating condition that affects the lungs and airways. It is characterized by persistent bronchitis, a condition exemplified by the inflammation of the bronchial tubes, the hypersecretion of mucus, emphysema, and the destruction of the airway
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Chronic obstructive pulmonary disease (COPD) is a chronic, debilitating condition that affects the lungs and airways. It is characterized by persistent bronchitis, a condition exemplified by the inflammation of the bronchial tubes, the hypersecretion of mucus, emphysema, and the destruction of the airway parenchyma. The combination of these conditions leads to persistent tissue damage, pulmonary fibrosis, and ongoing inflammation of the airways. The inflammatory response in COPD is a complex process that is orchestrated by a wide range of immune cells. These include lung epithelial cells, monocytes, macrophages, neutrophils, eosinophils, and T and B lymphocytes, among others. These cells work together to produce a wide range of inflammatory biomarkers that are involved in the pathogenesis of COPD. Some of the key inflammatory biomarkers that have been identified in COPD include a variety of cytokines, the C-reactive protein/serum albumin ratio, fibrinogen, soluble receptor for advanced glycation endproducts, club/clara cells in the lungs with a molecular weight of 16 kDa, surfactant protein D, adiponectin, reactive oxygen species, and proteases. This review aims to provide a comprehensive overview of the role of immune cells and key inflammatory biomarkers in the development and progression of COPD. It will delve into the intricacies of the inflammatory response in COPD, exploring the various cell types and biomarkers that are involved in this process. By understanding the underlying mechanisms that drive COPD, we can better develop targeted treatments that can help to alleviate the symptoms of COPD.
Full article
(This article belongs to the Special Issue The Role of Cytokines and Autoantibodies Against Cytokines in Health and Disease)
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Open AccessArticle
Preliminary Evidence of Enhanced Immunogenicity of Hepatitis B Virus Vaccines When Co-Administered with Calcium Phosphate, Aluminum Hydroxide, and Cytosine Phospho-Guanine Oligodeoxynucleotides Combined Adjuvant in BALB/c Mice
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Oumou Ouattara, Josephine W. Kimani and James H. Kimotho
Immuno 2025, 5(1), 12; https://doi.org/10.3390/immuno5010012 - 14 Mar 2025
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Hepatitis B virus (HBV) infection is a major public health risk. Despite the introduction of successful vaccines, which are normally single adjuvanted, there are still some drawbacks, including non-responsiveness in certain groups, short durability of immunity, inadequate protection, and the need for additional
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Hepatitis B virus (HBV) infection is a major public health risk. Despite the introduction of successful vaccines, which are normally single adjuvanted, there are still some drawbacks, including non-responsiveness in certain groups, short durability of immunity, inadequate protection, and the need for additional doses to be addressed. This study aimed to develop an optimized combination of Cytosine-phosphate-Guanine Oligonucleotides (CPG-ODN2395, CPG-ODN-18281-2 23 mer) and calcium phosphate, and to assess its immunogenicity and toxicity when co-administrated with the commercial HBV vaccine (BEVAC, containing aluminum hydroxide) and an in-house aluminum hydroxide-adjuvanted HBs purified antigen in Balb/c mice. Tail blood was collected from vaccinated Balb/c mice on days 14 and 28 post-immunization to determine the antibody secretion level using an enzyme-linked immunosorbent assay (ELISA). The Tumor Necrosis Factor (TNF-a) and interleukin-6 (IL-6) cytokine expression levels were assessed through real-time PCR, and the safety profile was checked through biochemical and hematological analysis. Our results showed that the combination of CPG-ODN2395, CPG-ODN 18281-2 23 mer, and CAP significantly enhanced the IgG antibody secretion level (p < 0.0001), which also showed a significant increase in IL-6 expression (p < 0.0001). The safety evaluations revealed no adverse impact on liver and kidney function, with normal ALT, AST, urea, and creatinine levels (p < 0.55). Hematological assessments revealed stable parameters across all groups. This study concludes that combining CpG ODNs and calcium phosphate adjuvants with hepatitis B vaccinations has the potential to enhance a stronger immunological response to hepatitis B infection than single adjuvants. These results highlight the promise of this innovative adjuvant system, necessitating more research in clinical environments to increase vaccine effectiveness and sustained protection against HBV.
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Open AccessReview
Anti-Inflammatory and Anti-Oxidative Effects of GLP1-RAs and SGLT2i: The Guiding Star Towards Cardiovascular Protection in Type 2 Diabetes
by
Livia M. R. Marcon and Alessio Mazzieri
Immuno 2025, 5(1), 11; https://doi.org/10.3390/immuno5010011 - 14 Mar 2025
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Type 2 diabetes mellitus (T2DM) is a chronic and progressive dysmetabolic condition related to several complications, including cardiovascular disease, whose incidence is increasing worldwide. Sodium–glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1-RAs) are two new molecules recently made available
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Type 2 diabetes mellitus (T2DM) is a chronic and progressive dysmetabolic condition related to several complications, including cardiovascular disease, whose incidence is increasing worldwide. Sodium–glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1-RAs) are two new molecules recently made available for T2DM treatment, with the aim of reducing hyperglycemia. Recent evidence has also highlighted that in addition to the glucose-lowering action, both SGLT2i and GLP1-RAs ensure significant beneficial effects in reducing cardiovascular damage in T2DM patients. Interestingly, these benefits cannot be exclusively attributed to the improved glycemic control. Indeed, experimental and clinical studies have shed light on the protective role of SGLT2i and GLP-1RAs against inflammation and oxidative stress, especially in the heart and vasculature. In our review we elucidate the potential cardiovascular benefits provided by SGLT2i and GLP1-RAs to T2DM subjects by exploring the molecular pathways involved in the process of cardiovascular protection.
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Open AccessReview
The Microbiome, Inflammation, and GVHD Axis: The Balance Between the “Gut” and the Bad
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Paula Pinzon-Leal, Hernando Gutierrez-Barbosa, Sandra Medina-Moreno and Juan C. Zapata
Immuno 2025, 5(1), 10; https://doi.org/10.3390/immuno5010010 - 7 Mar 2025
Abstract
Hematopoietic stem cell transplantation is one of the most intricate immune therapies used for patients with hematological diseases or immune disorders. In addition to the inherent immunosuppression from their primary condition, many of these patients usually receive cytotoxic chemotherapy, radiation therapy, broad-spectrum antibiotics,
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Hematopoietic stem cell transplantation is one of the most intricate immune therapies used for patients with hematological diseases or immune disorders. In addition to the inherent immunosuppression from their primary condition, many of these patients usually receive cytotoxic chemotherapy, radiation therapy, broad-spectrum antibiotics, or experience extended nutritional perturbations. These factors collectively lead to inflammation and the disruption of gut microbiota. Additionally, about 40–60% of patients undergoing fully HLA-matched allogeneic transplantation are expected to develop acute graft-versus-host disease (aGVHD), even with prophylactic measures such as calcineurin inhibitors, methotrexate/mycophenolate, or post-transplant cyclophosphamide treatment. Recent research has elucidated the complex interplay between immune effectors in the gastrointestinal tract and microbial populations within a proinflammatory peri-transplant environment, revealing its significant effect on survival and post-transplant complications such as aGVHD. This review will explore the relationship between dysbiosis during allogeneic transplantation and mechanisms that can help clarify the link between gut microbiota and the risk of GVHD, along with emerging therapeutic strategies aimed at addressing dysbiosis during hematopoietic stem cell transplantation.
Full article
(This article belongs to the Section Transplantation Immunology)
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Open AccessReview
A Concise Review of the Role of the NKG2D Receptor and Its Ligands in Cancer
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Elitsa Boneva, Velizar Shivarov and Milena Ivanova
Immuno 2025, 5(1), 9; https://doi.org/10.3390/immuno5010009 - 2 Mar 2025
Abstract
The immune system’s ability to detect and eliminate transformed cells is a critical factor in suppressing cancer development. However, immune surveillance in tumors is often disrupted by various immune escape mechanisms, many of which remain poorly understood. The Natural Killer Group 2D (NKG2D)
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The immune system’s ability to detect and eliminate transformed cells is a critical factor in suppressing cancer development. However, immune surveillance in tumors is often disrupted by various immune escape mechanisms, many of which remain poorly understood. The Natural Killer Group 2D (NKG2D) receptor is an activating receptor expressed on natural killer (NK) cells and cytotoxic T lymphocytes. It can recognize and bind with varying affinities to a wide range of structurally diverse ligands, including MHC class I chain-related proteins A and B (MICA and MICB) and members of the ULBP family (ULBP1-6). The expression of these ligands plays a crucial role in immune antitumor responses and cancer immunoevasion mechanisms. Some evidence suggests that functional polymorphisms in the NKG2D receptor and the genes encoding its ligands significantly influence HLA-independent cancer immunosurveillance. Consequently, the NKG2D-NKG2D ligands (NKG2DLs) axis represents a promising target for developing novel therapeutic strategies. This review aims to provide a general overview of the role of NKG2D and its ligands in various malignancies and explore their potential in advancing personalized cancer treatment protocols.
Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
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Open AccessReview
Super-Charged Natural Killer Cells: A Promising Immunotherapeutic Strategy for Oral Cancer
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Kawaljit Kaur and Anahid Jewett
Immuno 2025, 5(1), 8; https://doi.org/10.3390/immuno5010008 - 25 Feb 2025
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NK cells have traditionally been classified as effectors of innate immunity, even though they also exhibit some features of adaptive immunity such as memory. NK cells contribute to the lysis and growth inhibition of cancer, mediating direct cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC)
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NK cells have traditionally been classified as effectors of innate immunity, even though they also exhibit some features of adaptive immunity such as memory. NK cells contribute to the lysis and growth inhibition of cancer, mediating direct cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC) and regulating the functions of other immune cells, respectively. NK cells regulate the function of other immune cells via the release of inflammatory cytokines and chemokines. Currently, NK cell therapeutics in oral cancer have been less efficient due to several limitations, as follows: (a) lower percentages of NK cells in peripheral blood immune cells; (b) limited survival and decreased function of NK cells, especially in the tumor microenvironment; and (c) a lack of tools or methodologies to expand and activate NK cells to the levels that are required for the effective targeting of oral cancer. To overcome these limitations, we established and demonstrated a novel technology for activating and expanding highly functional NK cells coined as supercharged NK (sNK) cells. This review summarizes the characteristics of sNK cells and highlights their superior anti-cancer activity when compared to primary activated NK cells.
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Open AccessArticle
Applications of Multiplex Immunohistochemistry in Evaluating Spatiotemporal Heterogeneity of T Cells
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Mercedes Machuca-Ostos, Tim de Martines, Kanako Yoshimura, Junichi Mitsuda, Sumiyo Saburi, Alisa Kimura, Hiroki Morimoto, Koichi Yoshizawa, Nana Sakurai, Nanako Murakami, Kayo Kitamoto, Makoto Yasuda, Yoichiro Sugiyama, Hiroshi Ogi, Saya Shibata, Aya Miyagawa-Hayashino, Eiichi Konishi, Kyoko Itoh, Takahiro Tsujikawa and Shigeru Hirano
Immuno 2025, 5(1), 7; https://doi.org/10.3390/immuno5010007 - 17 Feb 2025
Abstract
T cell phenotypes and kinetics are emerging as crucial factors associated with immunotherapeutic responses in a wide range of solid cancer types. However, challenges remain in understanding the spatial and temporal profiles of T cells with differential phenotypes due to difficulties in single-cell
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T cell phenotypes and kinetics are emerging as crucial factors associated with immunotherapeutic responses in a wide range of solid cancer types. However, challenges remain in understanding the spatial and temporal profiles of T cells with differential phenotypes due to difficulties in single-cell analysis with preserved tissue structures. Here, we provide an optimized 12-marker multiplex immunohistochemical (IHC) panel and single-cell-based quantitative assessment to identify the spatial distributions of T cell phenotypes in formalin-fixed paraffin-embedded sections. This panel revealed differential T cell populations with spatial localizations in human tonsil tissue, where the percentages of CD8+ T cell-expressing programmed death receptor-1 (PD-1), T cell immunoglobulin and mucin domain 3 (TIM3), and other T cell phenotypic markers vary by tonsillar tissue components such as follicles, parenchyma, and epithelium. A specimen from salivary gland adenocarcinoma during hyper-progression, followed by anti-PD-1 treatment, exhibited the exclusion of CD8+ T cells from the intratumoral regions. Although the vast majority of peritumoral CD8+ T cells exhibited proliferative effector T cell phenotypes with PD-1−TIM3−Ki67+CD45RA+, intratumoral CD8+ T cells showed exhausted phenotypes with PD-1+TIM3− and increased Eomes expression, which might be related to poor therapeutic response in this case. To verify these findings in the context of temporal changes, we analyzed six longitudinal samples from a single patient with maxillary sinus cancer, observing increased T cell exhaustion along with metastasis and progression. Together, highly multiplexed IHC can be applied to analyze the spatiotemporal phenotypes of T cells, potentially contributing to the understanding of the mechanisms of resistance to immunotherapy.
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(This article belongs to the Special Issue Next-Generation Cancer Immunotherapy)
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Open AccessReview
Advances in Synthetic Immunology for Targeted Treatment of Systemic Autoimmune Diseases: Opportunities, Challenges, and Future Directions
by
Galih Januar Adytia, Henry Sutanto, Laras Pratiwi and Deasy Fetarayani
Immuno 2025, 5(1), 6; https://doi.org/10.3390/immuno5010006 - 25 Jan 2025
Cited by 2
Abstract
Systemic autoimmune diseases (SAIDs) affect millions worldwide, presenting significant clinical challenges due to their complex pathogenesis and limited treatment options. Traditional immunosuppressive therapies, while effective, often lack precision, leading to significant side effects and inadequate disease control. Recent advances in synthetic immunology offer
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Systemic autoimmune diseases (SAIDs) affect millions worldwide, presenting significant clinical challenges due to their complex pathogenesis and limited treatment options. Traditional immunosuppressive therapies, while effective, often lack precision, leading to significant side effects and inadequate disease control. Recent advances in synthetic immunology offer promising avenues for precise, targeted interventions in SAIDs. This review examines the latest innovations in synthetic immunology for treating autoimmune diseases, focusing on engineered immune cells, synthetic biologics, and gene-editing technologies. It explores the therapeutic potential of these approaches to modulate immune tolerance, reduce systemic inflammation, and enhance patient-specific treatment efficacy. However, despite these promising developments, challenges remain, including immune system complexity, safety concerns, and regulatory hurdles that may hinder clinical translation. This review aims to consolidate current advancements, address existing barriers, and outline potential future directions for synthetic immunology in autoimmune disease management, highlighting synthetic immunology’s role in transforming the therapeutic landscape for SAIDs.
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(This article belongs to the Section Synthetic Immunity and Immune Engineering)
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Open AccessReview
Verification of Immune Debts in Children Caused by the COVID-19 Pandemic from an Epidemiological and Clinical Perspective
by
Masayuki Nagasawa
Immuno 2025, 5(1), 5; https://doi.org/10.3390/immuno5010005 - 25 Jan 2025
Abstract
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Social behavior restrictions, social distancing, and promotion of non-pharmaceutical interventions (NPIs) during the COVID-19 pandemic have significantly reduced the incidence of many epidemic infections in the world, especially in children. Resurges of infectious diseases vary depending on the biological characteristics of each infectious
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Social behavior restrictions, social distancing, and promotion of non-pharmaceutical interventions (NPIs) during the COVID-19 pandemic have significantly reduced the incidence of many epidemic infections in the world, especially in children. Resurges of infectious diseases vary depending on the biological characteristics of each infectious pathogen and differences in culture, lifestyle, and infection control mitigation policies by country or region. Although the gapping of infectious disease outbreaks can cause children who were uninfected during that period to become more susceptible to infection after the pandemic, resulting in a slightly older age of infected children, there are no conclusive reports that suggest a definite impact on the development of children’s immune maturation or its balance. Insufficient immune challenges in early life may influence the risk of developing immune-mediated conditions such as allergies or autoimmune diseases later in life, though evidence for this is still emerging. Future observational studies are needed to determine the long-term impact of the epidemic gap caused by the COVID-19 pandemic as well as the long-term impact of COVID-19 infection itself on the immune function or balance of children.
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Open AccessArticle
Turning the Tables: Loss of Adaptive Immunity Reverses Sex Differences in Tuberculosis
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David Hertz, Lars Eggers, Linda von Borstel, Torsten Goldmann, Hanna Lotter and Bianca E. Schneider
Immuno 2025, 5(1), 4; https://doi.org/10.3390/immuno5010004 - 4 Jan 2025
Abstract
Sex-based differences in innate immunity may play a crucial role in susceptibility to and progression of tuberculosis (TB), a disease that disproportionately affects men. This study aimed to examine whether early host–pathogen interactions contribute to the heightened vulnerability of males to Mycobacterium tuberculosis
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Sex-based differences in innate immunity may play a crucial role in susceptibility to and progression of tuberculosis (TB), a disease that disproportionately affects men. This study aimed to examine whether early host–pathogen interactions contribute to the heightened vulnerability of males to Mycobacterium tuberculosis (Mtb) infection. Using recombination activating gene 2 knockout (RAG2 KO) mice, which lack adaptive immunity, we were able to isolate and analyze innate immune responses to Mtb without the influence of T and B cells. Surprisingly, and in stark contrast to wild-type mice that reflect the male bias as observed in humans, female RAG2 KO mice were more susceptible to Mtb than their male counterparts. Increased lung CFU in females was accompanied by a significant rise in inflammation, indicated by elevated levels of inflammatory cytokines and chemokines, as well as a massive influx of neutrophils into the lungs. In contrast, male mice exhibited higher levels of IFN-γ and CCL5, along with a greater presence of NK cells in their lungs, suggesting that, in the absence of adaptive immunity, males benefit from a more robust NK cell response, potentially offering greater protection by better controlling inflammation and slowing disease progression.
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(This article belongs to the Section Innate Immunity and Inflammation)
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Open AccessArticle
Changes in Analytes Related to Immunity in the Saliva of Pigs After Vaccination Against Lawsonia intracellularis
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Andrea Martínez-Martínez, Manuel Toledo, Emilio Ruiz, Simón García, Anabel Fernández, José Joaquín Cerón, Rut Menjon, María Teresa Tejedor, Elena Goyena and Alberto Muñoz-Prieto
Immuno 2025, 5(1), 3; https://doi.org/10.3390/immuno5010003 - 2 Jan 2025
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Lawsonia intracellularis is a Gram-negative, intracellular bacterium that can infect several animal species. In pigs, the bacteria cause porcine proliferative enteropathy, or ileitis. The wide spread of the pathogen produces a large impact on pig production worldwide. Saliva is a source of biomarkers
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Lawsonia intracellularis is a Gram-negative, intracellular bacterium that can infect several animal species. In pigs, the bacteria cause porcine proliferative enteropathy, or ileitis. The wide spread of the pathogen produces a large impact on pig production worldwide. Saliva is a source of biomarkers that can help to monitor changes in the immune system after vaccination. The purpose of this study was to study the changes in haptoglobin (Hp), immunoglobulin G (IgG), and adenosine deaminase (ADA) in saliva after vaccination against Lawsonia intracellularis. In addition, productivity parameters were analysed to evaluate if vaccination and changes in salivary analytes could be associated with changes in these parameters. The pigs vaccinated against Lawsonia showed an improvement in the productive parameters and a reduction in food conversion and frequency of diseases. In addition, they showed lower values of Hp (p = 0.011), IgG (p < 0.01), and ADA (p < 0.003) in saliva during the first two months of the fattening period compared to non-vaccinated pigs. It could be concluded that in our experimental conditions, the vaccination against Lawsonia intracellularis produced a significant decrease in biomarkers of the immune response in saliva compared with the non-vaccinated pigs. This would indicate a reduction in the activation of the immune system, which could be postulated to be due to the increased defence ability of the organism against pathogens. This reduced activation of the immune system can lead to better food conversion and an increase in the productive parameters of these pigs. Overall, this report opens a new window for the possible use of saliva for non-invasive evaluation of the immune system after vaccination in pigs.
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