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 28.1 days after submission; acceptance to publication is undertaken in 5.5 days (median values for papers published in this journal in the first 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
RGM Family Involved in the Regulation of Hepcidin Expression in Anemia of Chronic Disease
Immuno 2024, 4(3), 266-285; https://doi.org/10.3390/immuno4030017 - 28 Aug 2024
Abstract
The persistent production of inflammatory cytokines causes anemia of chronic disease (ACD). Playing a central role in the pathophysiology of ACD is hepcidin, a key regulator of iron metabolism. The regulation of hepcidin expression is a complex process intricately controlled by multiple pathways.
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The persistent production of inflammatory cytokines causes anemia of chronic disease (ACD). Playing a central role in the pathophysiology of ACD is hepcidin, a key regulator of iron metabolism. The regulation of hepcidin expression is a complex process intricately controlled by multiple pathways. These include the BMP/SMAD, the HFE–TFR2, and the IL-6/STAT3 pathway, each playing a significant role in this regulation. We detail the critical role of the repulsive guidance molecule (RGM) family, especially hemojuvelin (HJV/RGMc), in regulating hepcidin expression in ACD. HJV functions as a co-receptor for BMPs and positively regulates hepcidin expression. RGMa and RGMb may also regulate hepcidin expression and inflammatory responses. RGM family proteins play essential roles in the interplay between inflammation, iron metabolism, and the immune system, and elucidating them could lead to a better understanding of the pathophysiology of ACD and the development of new therapeutic strategies.
Full article
(This article belongs to the Section Innate Immunity and Inflammation)
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Open AccessArticle
Impaired Coordination of the Ciliary Movement in Patients with Chronic Rhinosinusitis with Nasal Polyps: The Role of Decreased Planar Cell Polarity Protein Expression
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Sakura Hirokane, Tomohiro Kawasumi, Sachio Takeno, Yukako Okamoto, Seita Miyamoto, Rikuto Fujita, Chie Ishikawa, Takashi Oda, Yuichiro Horibe, Takashi Ishino, Takao Hamamoto, Tsutomu Ueda and Koji Ikegami
Immuno 2024, 4(3), 247-265; https://doi.org/10.3390/immuno4030016 - 21 Aug 2024
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The planar cell polarity (PCP) of epithelial ciliated cells is essential for effective mucociliary clearance (MCC) in the sinonasal mucosa. We hypothesize that MCC coordination is impaired in nasal polyp (NP) mucosae due to the suppressed expression of a series of CPLANE (ciliogenesis
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The planar cell polarity (PCP) of epithelial ciliated cells is essential for effective mucociliary clearance (MCC) in the sinonasal mucosa. We hypothesize that MCC coordination is impaired in nasal polyp (NP) mucosae due to the suppressed expression of a series of CPLANE (ciliogenesis and planar cell polarity effector) complex proteins in chronic rhinosinusitis (CRS) patients. To investigate this hypothesis, we subjected sinonasal mucosal samples to live video recording to measure mucociliary transport velocity (MCTV) and scanning electron microscopy to evaluate surface morphology. The expression and distribution of a panel of PCP proteins, e.g., WDPCP and FUZ, were investigated in relation to inflammatory cytokine levels and clinical features. The mean MCTV of NP mucosae was significantly lower than that of the inferior turbinate mucosae. The CRS group with NPs (CRSwNP group) (n = 28) showed increased expression of IL-13 and CCL26 mRNA compared to CRS patients without NPs (n = 25) and controls (n = 30). WDPCP and FUZ mRNA levels were significantly decreased in NP mucosae compared to ethmoid sinus mucosae in CRSwNP patients. WDPCP protein distribution was reduced in the cytoplasmic region of ciliated cells in CRSwNP patients. We conclude that suppression of WDPCP in ciliated cells is responsible for the impaired MCC of nasal polyps with type-2 inflammation. This mechanism might explain the decreased clearance and the potential for worsening symptoms of CRSwNP.
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Open AccessReview
Interplay between Multisystem Inflammatory Syndrome in Children, Interleukin 6, Microbiome, and Gut Barrier Integrity
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Ali Zari, Elrashdy M. Redwan, Mikolaj Raszek, David Cowley, Altijana Hromić-Jahjefendić, Vladimir N. Uversky, Mark Fabrowski, Carlo Brogna, Marina Piscopo and Alberto Rubio-Casillas
Immuno 2024, 4(3), 226-246; https://doi.org/10.3390/immuno4030015 - 18 Aug 2024
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A severe consequence of SARS-CoV-2 infection that manifests as systemic inflammation and multi-organ involvement is called Multisystem Inflammatory Syndrome in Children (MIS-C). This review examines the possible relationship between gut barrier integrity, the microbiome, dysregulation of interleukin 6 (IL-6) signaling, and MIS-C. Clinical
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A severe consequence of SARS-CoV-2 infection that manifests as systemic inflammation and multi-organ involvement is called Multisystem Inflammatory Syndrome in Children (MIS-C). This review examines the possible relationship between gut barrier integrity, the microbiome, dysregulation of interleukin 6 (IL-6) signaling, and MIS-C. Clinical and biochemical features of MIS-C are comparable to those of other hyper-inflammatory syndromes, suggesting a dysregulated immune response. One possible explanation for the systemic inflammation seen in MIS-C patients is the SARS-CoV-2-induced dysregulation of the IL-6 signaling pathway. In addition, new data suggest a reciprocal link between gut barrier integrity and IL-6. SARS-CoV-2 exhibits bacteriophage-like behavior, highlighting the role of bacteria as a reservoir for the virus and emphasizing the importance of understanding the bacteriophagic mechanism of the virus in fecal–oral transmission. The increased translocation of viral products and bacterial toxins may result from disrupting the intestinal barrier and cause systemic inflammation. On the other hand, systemic inflammation can weaken the integrity of the intestinal barrier, which feeds back into the loop of immunological dysregulation. In the context of MIS-C, understanding the interaction between SARS-CoV-2 infection, IL-6, and gut barrier integrity may shed light on the etiology of the disease and guide treatment options. Since children with gut dysbiosis may be more susceptible to MIS-C, it is critical to reinforce their microbiome through probiotics supplementation, and plant-fiber-rich diets (prebiotics). Early antibiotic treatment and the use of zonulin antagonists should also be considered.
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Open AccessReview
Role of Micronutrients in the Response to SARS-CoV-2 Infection in Pediatric Patients
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Alexis Hipólito García, Francis Isamarg Crespo, Soriuska José Mayora, Wendy Yackeline Martinez, Inírida Belisario, Christian Medina and Juan Bautista De Sanctis
Immuno 2024, 4(3), 211-225; https://doi.org/10.3390/immuno4030014 - 31 Jul 2024
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Nutrition is essential in developing and maintaining a robust immune system and is vital for immune homeostasis. The pediatric population is particularly vulnerable to dietary changes, as their growth and development require a high energy intake. Malnutrition in infants can have immediate and
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Nutrition is essential in developing and maintaining a robust immune system and is vital for immune homeostasis. The pediatric population is particularly vulnerable to dietary changes, as their growth and development require a high energy intake. Malnutrition in infants can have immediate and long-lasting effects, increasing the risk of morbidity and mortality. Under and overnutrition can slow down the immune response to infections, which can delay recovery. To effectively defend against SARS-CoV-2 infection and enhance viral clearance, it is essential to maintain a healthy diet that includes sufficient macro and micronutrients. Several studies, most of which have been performed in adults, have shown that vitamins such as C, B12, folate, D, and E, as well as the minerals selenium, copper, iron, zinc, and magnesium, can help reduce the symptoms and duration of an infection. Supplementation with micronutrients has been shown to help with childhood malnutrition and can contribute to a more favorable clinical course of COVID-19. In children with obesity, it is also essential to monitor cardiometabolic and thrombotic risks, based on data from studies in adults. This review analyses the impact of the nutritional status of pediatric patients with SARS-CoV-2 infection, its contribution to clinical severity, and potential therapeutic interventions.
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Open AccessReview
Immune Checkpoint Inhibitors: Fundamental Mechanisms, Current Status and Future Directions
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Abdullah Younis and John Gribben
Immuno 2024, 4(3), 186-210; https://doi.org/10.3390/immuno4030013 - 5 Jul 2024
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Immune checkpoint inhibitors (ICI) are a promising form of immunotherapy that have significantly changed the therapeutic landscape for many advanced cancers. They have shown unique clinical benefit against a broad range of tumour types and a strong overall impact on survival in studied
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Immune checkpoint inhibitors (ICI) are a promising form of immunotherapy that have significantly changed the therapeutic landscape for many advanced cancers. They have shown unique clinical benefit against a broad range of tumour types and a strong overall impact on survival in studied patient populations. However, there are still many limitations holding back this immunotherapy from reaching its full potential as a possible curative option for advanced cancer patients. A great deal of research is being undertaken in the hope of driving advancements in this area, building a better understanding of the mechanisms behind immune checkpoint inhibition and ultimately developing more effective, safer, and wider-reaching agents. Taking into account the current literature on this topic, this review aims to explore in depth the basis of the use of ICIs in the treatment of advanced cancers, evaluate its efficacy and safety, consider its current limitations, and finally reflect on what the future holds for this very promising form of cancer immunotherapy.
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Open AccessArticle
Synergistic Effect of Co-Administered SARS-CoV-2 Vaccines Improves Immune Responses in BALB/c Mice: A Preliminary Study
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Nshimirimana Jonas, Josephine Kimani, James Kimotho, Matthew Mutinda Munyao and Samson Muuo Nzou
Immuno 2024, 4(2), 172-185; https://doi.org/10.3390/immuno4020012 - 7 Jun 2024
Abstract
Various vaccine platforms have been approved for broad use to prevent the transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. However, these vaccines exhibit distinct differences in immunogenicity and efficacy, which decline after vaccination and are further exacerbated by the emergence
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Various vaccine platforms have been approved for broad use to prevent the transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. However, these vaccines exhibit distinct differences in immunogenicity and efficacy, which decline after vaccination and are further exacerbated by the emergence of virus variants and mutants. This study reports the immunization outcomes against the SARS-CoV-2 virus by assessing the immune responses and safety of different SARS-CoV-2 vaccines co-administered in BALB/c mice. Vaccine combinations comprising mRNA/adenovirus26-vector, mRNA/inactivated, adenovirus26-vector/inactivated, and mRNA/adenovirus26-vector/inactivated vaccines were prepared in optimized doses, and their activities upon immunization evaluated in comparison with individual mRNA, adenovirus26-vectored, and inactivated vaccines. Fourteen- and 28-days post-immunization, we measured spike-specific IgG response using Enzyme-Linked Immunosorbent Assay (ELISA), cytokine expression profiles through Quantitative real-time polymerase chain reaction (RT-PCR), and evaluated safety through histopathological examination. The mRNA/Vector/Inactivated group exhibited slightly higher anti-spike IgG levels, albeit not statistically significant (p > 0.132). Importantly, this regimen induced elevated IL-6 and IFN-γ mRNA expression levels (p < 0.0001) compared to immunization with individual vaccines. In summary, this study demonstrated that co-administering the mRNA/adenovirus26 vector/inactivated SARS-CoV-2 vaccines improved spike-specific IgG response, triggered significantly enhanced IL-6 and IFN-γ mRNA expression levels, and proved safe in mice.
Full article
(This article belongs to the Section Infectious Immunology and Vaccines)
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Open AccessArticle
Rosuvastatin Intervention in Patients with Chronic Hepatitis B (CHB) Expands CD14+ CD16− Classical Monocytes via Aryl Hydrocarbon Receptor (AHR)
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Mina Rahmati, Mojtaba Zare Ebrahimabad, Alale Langari, Ali Najafi, Shohreh Taziki, Alireza Norouzi, Mehrdad Teimoorian, Milad Khorasani and Saeed Mohammadi
Immuno 2024, 4(2), 159-171; https://doi.org/10.3390/immuno4020011 - 17 May 2024
Abstract
Chronic hepatitis B (CHB) poses treatment challenges, with treatment response and disease outcome often determined by the immune response, particularly mononuclear phagocytes. Monocytes can differentiate into various subpopulations influenced by AHR. Statins, known for inflammation modulation, may impact monocyte function via AHR activation.
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Chronic hepatitis B (CHB) poses treatment challenges, with treatment response and disease outcome often determined by the immune response, particularly mononuclear phagocytes. Monocytes can differentiate into various subpopulations influenced by AHR. Statins, known for inflammation modulation, may impact monocyte function via AHR activation. This study explored rosuvastatin (RSV)’s effects on monocyte subtypes, inflammatory markers, and AHR in CHB patients. Fifteen CHB patients were randomly assigned to receive either 20 mg RSV or a placebo daily for three months. Flow cytometry assessed CD14+ CD16− (classical), CD14+ CD16+ (intermediate), and CD14dim CD16+ (patrolling) monocyte subtypes, along with AHR levels in each subset. ELISA quantified cytokines IL-6, IFN-γ, IL-12, IL-10, TNF-α, TGF-β, and IL-1β. RSV expanded CD14+ CD16− classical and reduced CD14+ CD16+ intermediate monocytes in CHB patients while increasing AHR+ cell percentages in all subsets. RSV treatment upregulated key AHR target genes (Cyp1a1, Cyp1b1, and ARNT), indicating robust AHR signaling activation. It also reduced pro-inflammatory cytokine levels (IL-6, IFNγ, IL-12, TNF-α) and elevated anti-inflammatory cytokines (IL-10, TGF-β). Thus, RSV may modulate the immune response by altering monocyte subtypes in CHB patients via AHR activation.
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(This article belongs to the Section Innate Immunity and Inflammation)
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Open AccessSystematic Review
Systematic Review: JAK-STAT Regulation and Its Impact on Inflammation Response in ARDS from COVID-19
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Irasema Rodriguez and Kate J. F. Carnevale
Immuno 2024, 4(2), 147-158; https://doi.org/10.3390/immuno4020010 - 14 May 2024
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has had a global impact and resulted in millions of deaths worldwide. The course of the Janus kinase signaling transducers and activators (JAK-STAT) pathway is an important molecular pathway that is involved in the cellular
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has had a global impact and resulted in millions of deaths worldwide. The course of the Janus kinase signaling transducers and activators (JAK-STAT) pathway is an important molecular pathway that is involved in the cellular response to various cytokines and growth factors promoting an inflammatory response. The overactivation of the JAK-STAT signaling pathway in coronavirus disease 2019 (COVID-19) and its effect on acute respiratory distress syndrome (ARDS)-induced inflammatory processes was observed in various clinical articles that focused on JAK-STAT regulation regarding angiotensin converting enzyme 2 (ACE2) expression and cytokine storm release. Down-regulation of the JAK-STAT signaling pathway through inhibitors decreases the inflammatory response by decreasing cytokine storm release. However, the increased regulation of JAK-STAT in severe COVID-19 patients caused cytokines such as interferon alpha (IFN-α) to promote the phosphorylation of STATs. This response indicated an imbalance with JAK-STAT regulation and its inability to induce the transcription of interferon stimulated response elements. Furthermore, an increase in ACE2 regulation was noted to also increase JAK-STAT signaling, yet the down-regulation of JAK-STAT signaling can result in the overexpression of ACE2 by binding to SARS-CoV-2 and increasing STAT1 expression. Data suggest that inflammatory cytokines enhance the activation of ACE2 in endothelial cells via JAK-STAT pathway. Increasing the regulation of the JAK-STAT signaling pathway enhances the release of cytokines such as tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ), further expressing ACE2. The expression of ACE2 regulates STAT1 and STAT2 expression, leading to the up-regulation of the inflammasomal complexes in hyper-inflammatory responses from the JAK-STAT pathway. Through the review of various clinical reports, the effect of the JAK-STAT signaling pathway on ARDS-induced inflammatory response was observed and correlated with the expression of ACE2 and cytokine storm release in severe COVID-19 cases.
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Open AccessArticle
Anti-Inflammatory Efficacy of Resveratrol-Enriched Rice Callus Extract on Lipopolysaccharide-Stimulated RAW264.7 Macrophages
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Chaiwat Monmai, Jin-Suk Kim and So-Hyeon Baek
Immuno 2024, 4(2), 131-146; https://doi.org/10.3390/immuno4020009 - 3 Apr 2024
Cited by 2
Abstract
Resveratrol and its derivative piceid exhibit a wide spectrum of health-promoting bioactivities. A resveratrol-enriched variety of Dongjin rice (DJ526) has been developed by transfection of a resveratrol biosynthesis gene, and increased resveratrol content has been confirmed in seeds following germination. In the current
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Resveratrol and its derivative piceid exhibit a wide spectrum of health-promoting bioactivities. A resveratrol-enriched variety of Dongjin rice (DJ526) has been developed by transfection of a resveratrol biosynthesis gene, and increased resveratrol content has been confirmed in seeds following germination. In the current study, these resveratrol-enriched seeds were induced to produce callus, and callus extracts were evaluated for in vitro anti-inflammatory activity. Callus cultures contained greater amounts of resveratrol and piceid than DJ526 seeds, and treatment with DJ526 callus extract significantly reduced the lipopolysaccharide (LPS)-induced production of proinflammatory mediators nitric oxide and prostaglandin E2 by RAW264.7 macrophages. The inflammation-related nuclear factor kappa B and mitogen-activated protein kinase pathways were also inhibited in DJ526 callus extract-treated RAW264.7 cells, resulting in downregulation of proinflammatory factor genes COX-2, iNOS, IL-1β, IL-6, and TNF-α. Expression of the LPS-binding toll-like receptor-4 was also markedly reduced in DJ526 callus extract-treated cells compared to DJ callus extract-treated cells. These findings demonstrate increased resveratrol and piceid content by callus culture of DJ526 rice seeds and the potent anti-inflammatory activity of resveratrol-enriched callus extract.
Full article
(This article belongs to the Special Issue Anti-inflammatory and Immunomodulatory Medicinal Plants and Their Derived Immunomodulators)
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Open AccessCase Report
Fulminant Recurrent Thrombosis in a Patient with Catastrophic Antiphospholipid Syndrome and Its Thirty-Day Outcome
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Pierpaolo Di Micco, Maurizio Dorato, Maurizio Latte, Maria D’Antò, Vittorio Luiso and Gerolamo Sibilio
Immuno 2024, 4(1), 125-130; https://doi.org/10.3390/immuno4010008 - 4 Mar 2024
Abstract
Catastrophic antiphospholipid syndrome (CAPS) is a rare clinical form of antiphospholipid syndrome (APS) associated with life-threatening complications due to simultaneous thrombosis that may affect small and large vessels. It may be localized to the venous and/or arteries at the same time, and there
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Catastrophic antiphospholipid syndrome (CAPS) is a rare clinical form of antiphospholipid syndrome (APS) associated with life-threatening complications due to simultaneous thrombosis that may affect small and large vessels. It may be localized to the venous and/or arteries at the same time, and there are not available guidelines based on randomized clinical trials or large series. We here report a clinical case of CAPS with onset after resolution of oligo-symptomatic infection SARS-CoV-2, that had transient improvement with warfarin after recurrent thromboses occurred despite treatment off-label with low doses of low molecular weight heparin. Furthermore, we tried to trace a line by which a multidisciplinary team may set specific timing to have follow-up because of the high morbidity, mortality, and prolonged time of hospitalization.
Full article
Open AccessArticle
A Serological Multiplexed Immunoassay (MIA) Detects Antibody Reactivity to SARS-CoV-2 and Other Viral Pathogens in Liberia and Is Configurable as a Multiplexed Inhibition Test (MINT)
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Brien K. Haun, Albert To, Caitlin A. Williams, Aquena Ball, Karalyn Fong, Teri Ann S. Wong, Bode Shobayo, Julius Teahton, Lauren Ching, Varney Kamara, Davidetta M. Tekah, Peter Humphrey, John Berestecky, Vivek R. Nerurkar and Axel T. Lehrer
Immuno 2024, 4(1), 108-124; https://doi.org/10.3390/immuno4010007 - 3 Mar 2024
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The SARS-CoV-2 pandemic ignited global efforts to rapidly develop testing, therapeutics, and vaccines. However, the rewards of these efforts were slow to reach many low- to middle-income countries (LMIC) across the African continent and globally. Therefore, two bead-based multiplexed serological assays were developed
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The SARS-CoV-2 pandemic ignited global efforts to rapidly develop testing, therapeutics, and vaccines. However, the rewards of these efforts were slow to reach many low- to middle-income countries (LMIC) across the African continent and globally. Therefore, two bead-based multiplexed serological assays were developed to determine SARS-CoV-2 exposure across four counties in Liberia. This study was conducted during the summer of 2021 on 189 samples collected throughout Grand Bassa, Bong, Margibi, and Montserrado counties. Our multiplexed immunoassay (MIA) detected elevated exposure to SARS-CoV-2 and multiple variant antigens. Additionally, we detected evidence of exposure to Dengue virus serotype 2, Chikungunya virus, and the seasonal coronavirus NL63. Our multiplexed inhibition test (MINT) was developed from the MIA to observe antibody-mediated inhibition of SARS-CoV-2 spike protein binding to its cognate cellular receptor ACE-2. We detected inhibitory antibodies in the tested Liberian samples, which were collectively consistent with a convalescent serological profile. These complementary assays serve to supplement existing serological testing needs and may enhance the technical capacity of scientifically underrepresented regions globally.
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Open AccessReview
Exploring the Interplay between Fatty Acids, Inflammation, and Type 2 Diabetes
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Dequina A. Nicholas, Jacques C. Mbongue, Darysbel Garcia-Pérez, Dane Sorensen, Heather Ferguson Bennit, Marino De Leon and William H. R. Langridge
Immuno 2024, 4(1), 91-107; https://doi.org/10.3390/immuno4010006 - 1 Mar 2024
Cited by 1
Abstract
Around 285 million people worldwide currently have type 2 diabetes and it is projected that this number will be surpassed by 2030. Therefore, it is of the utmost importance to enhance our comprehension of the disease’s development. The regulation of diet, obesity, and
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Around 285 million people worldwide currently have type 2 diabetes and it is projected that this number will be surpassed by 2030. Therefore, it is of the utmost importance to enhance our comprehension of the disease’s development. The regulation of diet, obesity, and inflammation in type 2 diabetes is believed to play a crucial role in enhancing insulin sensitivity and reducing the risk of onset diabetes. Obesity leads to an increase in visceral adipose tissue, which is a prominent site of inflammation in type 2 diabetes. Dyslipidemia, on the other hand, plays a significant role in attracting activated immune cells such as macrophages, dendritic cells, T cells, NK cells, and B cells to visceral adipose tissue. These immune cells are a primary source of pro-inflammatory cytokines that are believed to promote insulin resistance. This review delves into the influence of elevated dietary free saturated fatty acids and examines the cellular and molecular factors associated with insulin resistance in the initiation of inflammation induced by obesity. Furthermore, it explores novel concepts related to diet-induced inflammation and its relationship with type 2 diabetes.
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(This article belongs to the Section Innate Immunity and Inflammation)
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Open AccessArticle
IL-12p40 Monomer: A Potential Player in Macrophage Regulation
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Brian Jeong and Kalipada Pahan
Immuno 2024, 4(1), 77-90; https://doi.org/10.3390/immuno4010005 - 23 Feb 2024
Abstract
Macrophages are myeloid phagocytic leukocytes whose functions are to protect against infections, mediate T-cell responses, and maintain tissue homeostasis. IL-12p40 monomer is a cytokine that is largely produced by macrophages, and it has, for the longest time, been considered a largely non-functional cytokine
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Macrophages are myeloid phagocytic leukocytes whose functions are to protect against infections, mediate T-cell responses, and maintain tissue homeostasis. IL-12p40 monomer is a cytokine that is largely produced by macrophages, and it has, for the longest time, been considered a largely non-functional cytokine of the IL-12 family. However, new research has emerged that demonstrates that this p40 monomer may play a bigger role in shaping immune environments. To shed light on the specific effects of p40 monomer on macrophages and their surrounding environment, we showed, through cell culture studies, qPCR, ELISA, and immunofluorescence analyses, that the direct administration of recombinant p40 monomer to RAW 264.7 cells and primary lung macrophages stimulated the production of both pro-inflammatory (TNFα) and anti-inflammatory (IL-10) signals. Accordingly, p40 monomer prevented the full pro-inflammatory effects of LPS, and the neutralization of p40 monomer by mAb a3-3a stimulated the pro-inflammatory effects of LPS. Furthermore, we demonstrated that the intranasal administration of p40 monomer upregulated TNFα+IL-10+ macrophages in vivo in the lungs of mice. Collectively, these results indicate an important immunoregulatory function of p40 monomer in the upregulation of both pro- and anti-inflammatory molecules in macrophages.
Full article
(This article belongs to the Section Autoimmunity and Immunoregulation)
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Open AccessReview
Immune Dysregulation and Current Targeted Biologics in Hidradenitis Suppurativa
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Rene Chen, Robyn Guo, Amy J. Petty and Tarannum Jaleel
Immuno 2024, 4(1), 57-76; https://doi.org/10.3390/immuno4010004 - 2 Feb 2024
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Hidradenitis Suppurativa (HS) is a debilitating cutaneous disease characterized by a vicious cycle of chronic inflammation and tissue destruction that stems from disruption of the skin microbiome and abnormal activation of both the innate and adaptive immune system. A hallmark of HS pathophysiology
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Hidradenitis Suppurativa (HS) is a debilitating cutaneous disease characterized by a vicious cycle of chronic inflammation and tissue destruction that stems from disruption of the skin microbiome and abnormal activation of both the innate and adaptive immune system. A hallmark of HS pathophysiology is dysregulation of both the innate and adaptive immune system. The role of immune system dysregulation in HS development has motivated researchers to explore the utility of biologic immunomodulators. In 2015, adalimumab, a tumor necrosis factor-α inhibitor, was approved by the Food and Drug Administration (FDA) for treatment of moderate-to-severe HS in the US. In 2023, secukinumab, an interleukin-17A (IL-17A) inhibitor, was approved by the European Medicines Agency for treatment of moderate-to-severe HS in Europe. Ongoing clinical trials have shown promising clinical responses to targeted therapies against other pro-inflammatory cytokines including IL-17, IL-12, IL-1, IL-36, IL-6, IL-10, interferon γ, C5a, and Janus kinase (JAK). We provide an update on the efficacy and clinical usage of targeted biologics in HS treatment.
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Open AccessArticle
Markers for Immunological Resilience: Effects of Moderate- and High-Intensity Endurance Exercise on the Kinetic Response of Leukocyte Subsets
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Shirley W. Kartaram, Marc Teunis, Klaske van Norren, Mieke Smits, Laura M’Rabet, Martie C. M. Verschuren, Karin Mohrmann, Johan Garssen, Renger Witkamp and Raymond Pieters
Immuno 2024, 4(1), 43-56; https://doi.org/10.3390/immuno4010003 - 30 Jan 2024
Abstract
The kinetic responses of leukocyte subsets to exercise and their recovery may serve as indicators of immunological resilience. These time-dependent responses were investigated in healthy young men using a bicycle ergometer test. Fifteen recreationally active male cyclists (20–35 years, VO2max 56.9 ±
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The kinetic responses of leukocyte subsets to exercise and their recovery may serve as indicators of immunological resilience. These time-dependent responses were investigated in healthy young men using a bicycle ergometer test. Fifteen recreationally active male cyclists (20–35 years, VO2max 56.9 ± 3.9 mL kg−1 min−1) performed four exercise protocols with a 1 h duration in a cross-over design: at 70% of the maximal workload (Wmax) in a hydrated and a mildly dehydrated state, at 50% of the Wmax, and intermittently at 85/55% of the Wmax in blocks of 2 min. The numbers of lymphocytes, monocytes, neutrophils, eosinophils, basophils, thrombocytes, and NK cells (CD16 and CD56) were measured at different time points up to 24 h post-exercise. The total leukocyte counts and those of most subsets increased from the start of the exercise, peaking after 30–60 min of exercising. The neutrophil numbers, however, peaked 3 h post-exercise. The CD16brightCD56dim NK cells showed a 1.5-fold increase compared to the CD16brightCD56bright NK cells. Other than for MCP-1, no significant differences were found in the serum cytokine levels. Our results show that exercise intensity is reflected in different time-dependent changes in leukocyte subsets, which supports the concept that the exchange of immune cells between peripheral blood and tissues contributes to enhanced immune surveillance during strenuous exercise.
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(This article belongs to the Section Clinical/translational Immunology)
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Open AccessReview
The Role of Structural Bioinformatics in Understanding Tumor Necrosis Factor α-Interacting Protein Mechanisms in Chronic Inflammatory Diseases: A Review
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Luana Luiza Bastos, Diego Mariano, Rafael Pereira Lemos, Tatiane Senna Bialves, Carlo Jose Freire Oliveira and Raquel C. de Melo-Minardi
Immuno 2024, 4(1), 14-42; https://doi.org/10.3390/immuno4010002 - 15 Jan 2024
Abstract
Tumor necrosis factor α (TNF-α) is a multifunctional cytokine protein acknowledged as a vital mediator in cell differentiation, proliferation, and survival. Additionally, TNF-α is a crucial component of the host’s defense by mediating inflammatory and immune responses against various aggressive agents, including viruses,
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Tumor necrosis factor α (TNF-α) is a multifunctional cytokine protein acknowledged as a vital mediator in cell differentiation, proliferation, and survival. Additionally, TNF-α is a crucial component of the host’s defense by mediating inflammatory and immune responses against various aggressive agents, including viruses, bacteria parasites, and tumors. However, excessive production can be detrimental to the body and is also implicated in developing several inflammatory and immune-mediated disorders. Therefore, there is great interest in studying its role and its modulation, in various diseases, both in in vitro, in vivo, and in silico experiments. In this review, we evaluated the structures of proteins related to TNF-α available in public databases. In addition, we described the main antibodies blocking this cytokine and its applications and commented on the potential of naturally produced binding molecules, such as TNF-α-binding proteins produced by ticks. We also discuss the role of structural bioinformatics techniques in understanding the mechanisms of chronic inflammatory diseases related to TNF-α. We hope that the data presented in this review will be useful for studies that aim to better understand the mechanisms of the interactions of TNF-α with other proteins and will lead to new drugs or treatments.
Full article
(This article belongs to the Section Structural Immunology)
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Open AccessReview
Catastrophic Antiphospholipid Syndrome: A Review
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Carmine Siniscalchi, Manuela Basaglia, Michele Riva, Michele Meschi, Tiziana Meschi, Giampiero Castaldo and Pierpaolo Di Micco
Immuno 2024, 4(1), 1-13; https://doi.org/10.3390/immuno4010001 - 25 Dec 2023
Cited by 5
Abstract
Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombotic or obstetric events occurring in individuals who have persistent antiphospholipid antibodies. Catastrophic antiphospholipid syndrome (CAPS) is a rare and potentially fatal form of APS characterized by severe thrombotic complications occurring in multiple
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Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombotic or obstetric events occurring in individuals who have persistent antiphospholipid antibodies. Catastrophic antiphospholipid syndrome (CAPS) is a rare and potentially fatal form of APS characterized by severe thrombotic complications occurring in multiple organs over a short period of time or simultaneously. CAPS is associated with a high (50%) death rate. Infections, multi-organ failure, and cerebral and heart thrombosis represent the main complications of this syndrome. Generally, anticoagulants, glucocorticoids, therapeutic plasmapheresis (TPE), and intravenous immunoglobulin (IVIG) are used in combination for treatment. Multidisciplinary care involving different specialists from hematology, rheumatology, nephrology, infectious disease, critical care, and obstetrics is often required due to the complexity of the disease. Recent data emphasize the effectiveness of biologics such as anti-TNF-a monoclonal antibodies (adalimumab, certolizumab), anti-CD38 monoclonal antibody (daratumumab), BAFF/Blys inhibitor (belimumab), and BTK inhibitor (zanubrutinib) against CAPS. In order to understand the underlying causes of CAPS, one future possibility involves investigating and characterizing the hereditary and acquired risk factors associated with CAPS.
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(This article belongs to the Special Issue Recent Advances in Antiphospholipid Syndrome)
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Open AccessReview
Inflammatory Network of Liver Fibrosis and How It Can Be Targeted Therapeutically
by
Kirstin O. Lowe, Constantin E. Tanase, Susan Maghami, Leanne E. Fisher and Amir M. Ghaemmaghami
Immuno 2023, 3(4), 375-408; https://doi.org/10.3390/immuno3040023 - 28 Nov 2023
Cited by 2
Abstract
Liver fibrosis is a complex, dynamic process associated with a broad spectrum of chronic liver diseases and acute liver failure, characterised by the dysregulated intrahepatic production of extracellular matrix proteins replacing functional liver cells with scar tissue. Fibrosis progresses due to an interrelated
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Liver fibrosis is a complex, dynamic process associated with a broad spectrum of chronic liver diseases and acute liver failure, characterised by the dysregulated intrahepatic production of extracellular matrix proteins replacing functional liver cells with scar tissue. Fibrosis progresses due to an interrelated cycle of hepatocellular injury, triggering a persistent wound-healing response. The accumulation of scar tissue and chronic inflammation can eventually lead to cirrhosis and hepatocellular carcinoma. Currently, no therapies exist to directly treat or reverse liver fibrosis; hence, it remains a substantial global disease burden. A better understanding of the intricate inflammatory network that drives the initiation and maintenance of liver fibrosis to enable the rationale design of new intervention strategies is required. This review clarifies the most current understanding of the hepatic fibrosis cellular network with a focus on the role of regulatory T cells, and a possible trajectory for T cell immunotherapy in fibrosis treatment. Despite good progress in elucidating the role of the immune system in liver fibrosis, future work to better define the function of different immune cells and their mediators at different fibrotic stages is needed, which will enhance the development of new therapies.
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(This article belongs to the Section Clinical/translational Immunology)
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Open AccessArticle
High-Avidity Anti-Filovirus IgG Elicited Using Protein Subunit Vaccines Does Not Correlate with Protection
by
Caitlin A. Williams, Teri Ann S. Wong, Michael M. Lieberman, Jake Yalley-Ogunro, Mehtap Cabus, Sara Nezami, Fabian Paz, Hanne Andersen, Thomas W. Geisbert and Axel T. Lehrer
Immuno 2023, 3(4), 358-374; https://doi.org/10.3390/immuno3040022 - 24 Oct 2023
Abstract
Zaire ebolavirus (EBOV) poses a significant threat to public health due to its high case fatality rate and epidemic potential. This is further complicated by the lack of precise immune correlates of protection and difficulties in conducting in vivo animal studies due to
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Zaire ebolavirus (EBOV) poses a significant threat to public health due to its high case fatality rate and epidemic potential. This is further complicated by the lack of precise immune correlates of protection and difficulties in conducting in vivo animal studies due to species specificity of Ebola virus disease (EVD) and classification as a biosafety level 4 pathogen. Related ebolaviruses have also contributed to the public health threat; Uganda recently experienced an outbreak of Sudan ebolavirus, which also had a high case fatality rate. Vaccination targeting EBOV has demonstrated significant efficacy; however, the protective cellular and humoral responses at play are still poorly understood. Vaccination for vulnerable populations such as pregnant women, young children, and immunocompromised individuals is still limited. Understanding vaccine correlates of protection (vCOP) is key to developing alternative vaccination strategies for these groups. Components of immunity such as neutralizing antibody and cell-mediated immunity are likely responsible for protective responses; however, existing research fails to fully define their roles in protection. Here we investigated vaccine-elicited antibody avidity as a potential correlate of protection and to further characterize the contribution of antibody avidity in protective and nonprotective vaccine responses.
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(This article belongs to the Section Infectious Immunology and Vaccines)
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Open AccessReview
Monoclonal War: The Antibody Arsenal and Targets for Expanded Application
by
Eric H. Rosenn, Mickael Benhaim, Allison Siegel, David A. Stein, Joseph S. Leonard, Erik Katcher, Dania Halperin and Zachary Mostel
Immuno 2023, 3(3), 346-357; https://doi.org/10.3390/immuno3030021 - 20 Sep 2023
Abstract
Advancements in sequencing and screening technology have made monoclonal antibodies more accessible, cost-effective, and precise. These drugs effectively target pathogens and cancer cells and even regulate metabolic pathways by focusing on specific intermediates. Monoclonal antibodies play a key role in mitigating a rise
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Advancements in sequencing and screening technology have made monoclonal antibodies more accessible, cost-effective, and precise. These drugs effectively target pathogens and cancer cells and even regulate metabolic pathways by focusing on specific intermediates. Monoclonal antibodies play a key role in mitigating a rise in occupation-related cancers, neurodegenerative disorders, and multidrug-resistant organisms. Here, we review the origins, mechanisms, and applications of this important drug class and explore future avenues for research.
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(This article belongs to the Section Synthetic Immunity and Immune Engineering)
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