Immuno

Successful implantation requires a finely regulated endometrial microenvironment during the window of implantation. Chronic endometritis, defined by plasma cell infiltration, and stromal senescence, indicated by p16 expression, represent separate but potentially interacting mechanisms associated with impaired endometrial receptivity. The relationship between these processes remains poorly understood. We aim to examine whether stromal senescence is associated with plasma cell density and clustering in the human endometrium during the implantation window. Forty mid-luteal (LH+7) endometrial biopsies were retrospectively analyzed and stratified into low-senescence (<0.5% stromal p16⁺ cells, n = 20) and high-senescence (>3.5%, n = 20) groups. Plasma cells were identified by immunohistochemistry for MUM1 and CD138 and quantified using HALO^® software (version 3.4). Group comparisons were performed using Student’s t-test and chi-squared analysis. CD138⁺ plasma cells were significantly more abundant in high-senescence endometria than in low-senescence controls (0.065 ± 0.10 vs. 0.014 ± 0.027 cells/mm², p = 0.02). Only MUM1⁺ cells formed stromal clusters, which were more frequent in high-senescence samples (67% vs. 31%, p = 0.05). High endometrial stromal senescence during the implantation window is associated with increased plasma cell infiltration and clustering. This interplay may contribute to chronic endometritis and impaired receptivity, providing new insights into potential diagnostic and therapeutic strategies for reproductive failure. Full article

Hericium erinaceus is a medicinal mushroom valued in the wellness industry for its neuroprotective, immunomodulatory, and antioxidant activities. While many extracts and bioactive compounds from both mycelium and fruit bodies have been characterized, the mechanisms driving their effects are not fully understood. Here, the transcriptomic and protein-level effects of H. erinaceus mycelium (HDLM) in human peripheral blood mononuclear cells (PBMCs) were investigated, along with antioxidant and iron chelating activity. A commercially available H. erinaceus fruit body extract (FBE) claiming high β-glucan content was included in a subset of assays to compare immune-related outcomes between mycelial and fruit body constituents. HDLM activated a wide array of immune- and oxidative stress-related transcripts and pathways, exhibited significant antioxidant activity, and consistently reduced IL-1β, TNF-α, and IL-8 during LPS challenge while maintaining low basal cytokine expression, indicating targeted immunomodulatory activity. FBE almost doubled production of IL-1β when challenged by LPS, whereas HDLM significantly decreased production of this stress mediator. HDLM also demonstrated augmented iron chelating ability when compared to FBE. Depending on tissue source and preparation methods, different H. erinaceus materials may either potentiate or quench stress responses, highlighting the need for further bioactivity and safety comparisons across H. erinaceus supplements, particularly with respect to cytokine regulation under conditions of immune challenge. Full article

Unexplained infertility and idiopathic recurrent pregnancy loss (RPL) have a prevalence of 1–5% of women of reproductive age in different populations. There are a few reports comparing the circulating immune cell populations and subpopulations in these medical entities in admixed populations. The study aimed to assess the different leukocyte, mononuclear cell populations, and T lymphocyte subpopulations and HLADR expression, as a marker of activation, in an admixed group of Venezuelan women: 80 controls, 73 women with RPL (53 primary, 20 secondary), and 26 infertile (20 primary, six secondary). Endometriosis was clinically ruled out in all patients and controls. Total leukocytes were 10–12% higher (p < 0.0001) in the infertile group, while neutrophils were 11% in the infertility group (p < 0.0001). In contrast, lymphocytes, CD3CD4 cells, NK cells, and HLADR+ cells were elevated (10–15, 18–22, 50–60, and 700–800% increase, respectively) in all patient groups. Changes in B cell numbers and monocyte counts were also observed. HLADR expression was significantly increased (p < 0.0001) in T cells, CD56+ cells, and monocytes of all patients. In infertile patients, a correlation was recorded between HLADR and T memory cells. Marked differences in peripheral blood leukocytes, NK cells, monocytes, T-cell populations, and HLADR suggest a proinflammatory effect. HLADR can be used as a simple biomarker to monitor pharmacological treatment in these patients. Full article

T cells and B cells are central components of the adaptive immune system, orchestrating immune responses through a complex network of interactions. This review explores the dynamic interplay between T and B cells, focusing on their development, activation, and functional coordination in immune defense. T cells provide essential help to B cells through cytokine signaling and direct cell–cell interactions, facilitating antibody production and affinity maturation in germinal centers. Conversely, B cells contribute to antigen presentation and cytokine modulation, influencing T cell differentiation and function. The regulation of these interactions is critical for maintaining immune homeostasis, preventing autoimmunity, and enhancing vaccine efficacy. Dysregulation of T-B cell crosstalk is implicated in various immune disorders, including autoimmune diseases and immunodeficiencies. Recent advances in immunotherapy have targeted these pathways to modulate immune responses in conditions such as cancer, infections, and inflammatory diseases. This review synthesizes current knowledge on T and B cell physiology, highlighting emerging research on their cooperative mechanisms. Full article

Angioedema (AE) is a heterogeneous condition characterized by acute, localized, non-pitting edema of the skin, mucosa, and submucosal tissues, with potentially life-threatening airway involvement. This comprehensive review aims to provide an updated overview of the different AE subtypes, their pathogenesis, clinical presentation, diagnostic criteria, therapeutic strategies, and dental implications. A literature search of PubMed, MEDLINE, and Google Scholar was performed for articles published between 1950 and 2025, focusing on both bradykinin- and histamine-mediated forms. The findings highlight the importance of distinguishing histaminergic AE, which typically responds to antihistamines, corticosteroids, and epinephrine, from bradykinin-mediated AE, which requires targeted therapies such as C1 esterase inhibitor (C1-INH), icatibant, or kallikrein inhibitors. Subtypes including hereditary, acquired, and drug-induced AE are reviewed, with emphasis on diagnostic markers (C4, C1-INH, C1q) and recent genetic insights in HAE-nC1INH. In dental and surgical settings, invasive procedures may act as triggers, making prophylaxis with plasma-derived C1-INH and stress management strategies essential. In conclusion, accurate subtype recognition is crucial to guide therapy and perioperative care, and further research is needed to refine diagnostic algorithms and preventive strategies. Full article

Autoimmune disease (AD) is a breakdown of self-tolerance by the immune system and has a variety of clinical manifestations and complications across all organ systems. One of the targets for treatment of AD aims at reducing inflammation and upregulating factors that eliminate autoreactive cells. Intermittent fasting (IF) has recently gained popularity as a dietary intervention for weight management, but has also been found to interact and positively interfere with pathways involved in the pathophysiology of AD. Methods include searching in the PubMed and Google Scholar databases for reviews and clinical trials studying any relationships between AD and IF. The search results have identified a variety of anti-inflammatory effects IF has on the immune system that can potentially reduce AD severity and several trials specifically studying IF’s effects on type I diabetes (T1D), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and multiple sclerosis (MS). Based on the findings, IF has potential anti-inflammatory effects that could assist with decreasing AD severity. Future directions include studies to further determine safety and efficacy of IF with AD, broader investigations to include IF’s impact on a wide variety of ADs, an ideal time frame of how long patients should remain on IF, and any potential interactions IF may have on current drug therapies used to treat AD. This review also aims to encourage more human studies of IF and its application to AD given that many of these results are largely from in vitro, cellular and molecular, and animal studies. Full article

The exact role of nitric oxide (NO) in the complex interplay between the host and Trichinella spiralis (T. spiralis) parasite remains uncovered. While much has been revealed about the role of the inducible isoenzyme (iNOS) in different parasitic infections, research is slowly progressing toward understanding the neuronal enzyme (nNOS)-derived impacts on trichinosis. This study aims to clarify the dual nature of (NO) during the enteral phase of experimental trichinosis by examining the participation of both iNOS and nNOS in T. spiralis-infected mice. The experimental design included 48 male Swiss albino mice divided into six groups: (G1) negative control, (G2) infected control, (G3) infected–Albendazole-treated, (G4) infected-infected–L-arginine-treated, (G5) infected–Aminoguanidine-treated, and (G6) infected–7-Nitroindazole-treated. On the seventh day post-infection, the study groups underwent parasitological (adult worm count), histopathological, immunohistochemical, and biochemical assessments. Our results showed that (nNOS) predominance during the enteral phase of trichinosis enhanced parasitic clearance. Conversely, NO produced by iNOS was not essential for worm expulsion but contributed to T. spiralis-mediated enteropathy. Nitric oxide seems to play a puzzling role in T. spiralis infection. While (iNOS) is known for eliminating numerous infections, this is the first example we are aware of where the activity of the neuronal isoform (nNOS) is required in trichinosis. Full article

The clinical features and outcomes of adult acute leukemia (AL)-associated hemophagocytic lymphohistiocytosis (AL-HLH) remain insufficiently characterized. We retrospectively analyzed 45 adult patients diagnosed with AL-HLH between December 2019 and June 2023. Among 746 AL patients, 45 developed HLH, with 40 developing acute myeloid leukemia (AML), 4 developing acute lymphoblastic leukemia (ALL), and 1 developing mixed-phenotype acute leukemia (MPAL). According to the ELN 2022 criteria, 16 (35.6%) had favorable, 3 (6.7%) had interediate, and 26 (57.7%) had poor risk. At the time of HLH onset, seven (15.6%) patients were in composite complete remission (CCR), and 38 (84.4%) were in non-CCR states; 25 (55.6%) patients were newly diagnosed before induction chemotherapy. The HLH-94/04-based regimens (etoposide and dexamethasone) with or without ruxolitinib achieved an ORR (overall remission rate) of 82.2% and a CR rate of 66.7%. After anti-leukemic therapy, 60% (27/45) of patients achieved CCR for leukemia (including patients in CCR at HLH onset and those achieving CCR after treatment). Hematopoietic stem cell transplantation (HSCT) independently predicted sustained remission. The estimated overall rates at 6 and 12 months after HLH diagnosis were 73.1% and 59.2%, respectively. Multivariate Cox analysis identified failure to achieve CCR for leukemia as the only independent adverse prognostic factor. AL-HLH is an uncommon but severe complication that predominantly occurs in AML patients with poor-risk cytogenetics or active disease. Early recognition, effective HLH control, and achievement of CCR in AL are crucial for improving patient prognosis. Full article

Filarial parasites are long-lived organisms that cause extreme morbidity due to pathological manifestations, including lymphedema, hydrocele, and elephantiasis. Understanding the hosts’ immune responses to filarial parasites is crucial to developing new and effective anti-filarial treatments. The review thoroughly examines and summarises immunological modulation, evasion strategies, and filarial–host immune interactions to provide an updated knowledge of the immune evasion manoeuvres used by filarial parasites. An extensive literature search was conducted using databases such as PubMed, Google Scholar, ScienceDirect, Web of Science, and Scopus to identify articles published mostly between 2000 and 2025 that focus on the crucial molecular, cellular, and immunomodulatory strategies of filarial parasites. The immune evasion mechanisms include the modulation of effector T cells, induction of apoptosis in immune cells, the release of immunomodulatory proteins, and the induction of regulatory immune cell populations, thereby ensuring the mutual survival of both the parasite and the host. An antigen-specific T helper 2 (Th2) response and an increase in Interleukin-10 (IL-10) producing CD4+ T cells, along with a suppressed T helper 1 (Th1) response, are the key immunological characteristics of filarial pathogenesis. This antigen-specific T-cell hyporesponsiveness seems necessary for keeping the long-term infection going, which often involves large parasite densities. This review summarises filarial parasites’ mechanisms and strategies in regulating host immune responses and will facilitate future studies on the filarial pathogenesis, leading to the development of novel anti-filarial therapeutics. Full article

Background: Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease in which cytotoxic T cells contribute to tissue damage through dysregulated effector pathways. CD107a (LAMP-1) serves as a functional marker of CD8⁺ T-cell degranulation and may reflect disease-related alterations in cytotoxicity. Objective: To investigate the expression of CD107a on cytotoxic T cells in SLE patients and evaluate its relationship with disease activity and immunological features. Methods: Demographic, hematological, and immunological profiles of SLE patients and controls were compared. Flow cytometry was used to evaluate CD3⁺, CD3⁺CD8⁺, CD4⁺, double-negative T cells, and CD107a⁺CD8⁺ subsets. Correlations with disease activity and diagnostic performance were assessed. Results: SLE patients showed anemia, thrombocytopenia, and lymphopenia compared with controls. Immunophenotyping revealed significantly elevated CD3⁺CD8⁺, CD107a⁺CD8⁺ T cells in SLE, and reduced CD4⁺ counts. While CD107a⁺CD8⁺ levels were strongly elevated, they did not correlate with disease activity scores, suggesting persistent upregulation of CD107a expression independent of clinical severity. ROC curve analysis indicated that CD3⁺ and CD3⁺CD8⁺ subsets had diagnostic utility, while double-negative T cells showed additional value. Conclusion: SLE is associated with increased CD107a⁺CD8⁺ T cells, reflecting heightened basal expression of this degranulation marker regardless of disease activity level. These findings underscore the role of altered cytotoxic T-cell function in SLE immunopathogenesis and support CD107a as a potential biomarker of immune dysregulation. Full article

Killer-cell immunoglobulin-like receptors (KIRs) play a crucial role in the cytotoxic activity of natural killer (NK) cells, encompassing both inhibitory and activating types. A higher ratio of cytotoxic to inhibitory receptors may harm successful pregnancies by disrupting the uterine environment. Ongoing debates surround the impact of KIR gene variations on recurrent pregnancy loss (RPL) and infertility across populations. This study aimed to explore KIR gene polymorphisms in RPL and infertility among the Venezuelan admixed population. The Venezuelan population exhibits a genetic mix of Caucasian, African, and local Amerindian ancestry, distinguishing it from other Latin American admixed populations. This study included 100 controls and 86 patients: 73 women with idiopathic RPL (53 primary and 20 secondary) and 13 infertile patients (4 primary and 9 secondary). The frequency of activating receptors KIR2DS2 and KIR2DS3 was significantly lower (p < 0.05) in the whole patient group compared to controls. However, when analyzing the haplotypes and genotypes, the significance between patients and controls was lost. When comparing RPL and infertile patients, KIR2DS2, KIR2DL3, 2DL5, and 3DL1 were significantly less frequent in infertile women. In infertile women, KIR2DS3 frequency was increased compared to controls and RPL. The results suggest that the frequency of inhibitory receptors may differentiate patients with RPL and infertility. Further studies should ascertain the expression and function of KIRs in uterine NK cells in patients with RPL and infertility. Full article

Nearly 10% of IVF patients experience repeated implantation failure (RIF). Although several meta-analyses report improved outcomes following peripheral blood mononuclear cell (PBMC) administration, the uterine mechanisms remain poorly understood. We first analyzed PBMC composition and cytokine secretion in a preliminary cohort (n = 18), followed by endometrial immune profiling in a larger cohort (n = 70) before and after PBMC treatment. Embryo transfer was performed in 41 women, enabling the assessment of associations between immune profiles and implantation success. Successful implantation occurred in 16 of 41 embryo transfers (39%). PBMCs were predominantly composed of lymphocytes (60.7%), with T helper cells as the predominant T cell subset (Th/cytT ratio 1.44). Cytokine assays confirmed secretion of TNF-α, IL-6, IL-4, and IL-10. C-reactive protein levels remained below the threshold for systemic inflammation and were unaffected by PBMC administration. In the full cohort, PBMC infusion significantly enriched stromal macrophages and T helper cells, reflected by higher Th/T, Th/MΦ, and Th/cytotoxic T cell ratios and a reduced cytotoxic T/T cell ratio (all p ≤ 0.001). Importantly, women with successful implantation exhibited a significantly higher macrophage/T cell ratio (1.15 vs. 0.74; p = 0.024). These findings suggest that PBMC administration reshapes the endometrial immune landscape and that the macrophage/T cell ratio may serve as a promising biomarker of treatment efficacy. Full article

Celiac disease (CD) is a chronic autoimmune condition traditionally recognized for its gastrointestinal symptoms. However, growing evidence indicates that CD can also affect social and emotional health, particularly among children. This narrative review explores how the autoimmunity of CD may contribute to social–emotional dysregulation through mechanisms such as neuroinflammation, nutrient deficiencies, and disruption of the gut–brain axis. It summarizes the current literature on anxiety, attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and autism spectrum disorder (ASD), highlighting how immune dysregulation may influence children’s social–emotional wellbeing. Delayed diagnosis, poor dietary adherence, and ongoing inflammation were recognized among children with social–emotional dysregulation. While digestive problems are commonly recognized and treated, social–emotional dysregulation among children with CD is frequently overlooked. However, a gluten-free diet without a confirmed diagnosis of CD is not sufficient to improve social–emotional outcomes. Children presenting with social–emotional dysregulation and clinical features suggestive of CD should be screened using standard serology and, when indicated, biopsy. Starting a gluten-free diet (GFD) without a confirmed diagnosis is not recommended. While mechanistic pathways are described, most evidence remains observational and clinically descriptive, underscoring the need for longitudinal and experimental studies to understand the intersectionality of CD with social–emotional dysregulation. Full article

Micro- and nanoplastics (MNPs) are emerging environmental immunotoxins with widespread human exposure through ingestion, inhalation, and dermal contact. Detected in the placenta, lungs, blood, bone marrow, and brain, MNPs accumulate in immune organs where they disrupt innate and adaptive cell functions. This review aims to provide a comprehensive summary of the current knowledge on how MNPs affect the immune system at the cellular and molecular levels. Experimental evidence shows that MNPs impair macrophage phagocytosis, skew dendritic cell maturation, trigger neutrophil extracellular traps, and alter T and B cell responses. Mechanistically, these effects are driven by oxidative stress, mitochondrial dysfunction, and activation of key inflammatory signaling pathways, including NF-κB, MAPK, and NLRP3 inflammasome, leading to apoptosis, pyroptosis, and chronic low-grade inflammation. Furthermore, MNP-induced disruption of epithelial barriers and gut microbiota composition undermines immune tolerance and contributes to the pathogenesis of autoimmune conditions. Preclinical models provide evidence linking MNP exposure to exacerbation of diseases such as systemic lupus erythematosus, inflammatory bowel disease, and rheumatoid arthritis. However, human epidemiological data remain limited, highlighting the urgent need for standardized exposure protocols, advanced omics technologies, and longitudinal cohort studies are urgently needed to establish causal links and inform public health strategies. Full article

Embryo implantation requires a finely tuned immune balance at the maternal–fetal interface. Interferon tau (IFN-τ), a key immunomodulator in ruminant implantation, may have therapeutic potential in human reproduction. This study investigated its effects on peripheral blood mononuclear cells (PBMCs) in vitro and the subsequent impact on endometrial immune composition following intrauterine administration of these cells. The work was conducted in two stages. First, in vitro assays were performed with PBMCs from 20 patients with recurrent implantation failure (RIF) cultured with or without IFN-τ for 24 h. Cytokines (IL-10, IL-4, TNF-α, IL-6) were measured by ELISA, and T cell subsets (Th, cytT, Th1, Th2, Th9, Tfh, Th17, Treg) were analyzed by flow cytometry. IFN-τ increased IL-4 and reduced TNF-α and IL-6, indicating a Th2 profile shift. T-cell analysis revealed fewer cytT, Th1, Th9, and Th17 cells, more Th2 cells, and improved Th/Tk, Th1/Th2, and Th17/Treg ratios after IFN-τ. A second clinical study included 55 RIF patients who received intrauterine IFN-τ-modulated PBMCs. Post-treatment endometrial biopsies revealed more helper T cells and macrophages, with higher Th/total T, Th/cytT, and Th/macrophage ratios, suggesting a tolerogenic environment. Overall, IFN-τ modulates PBMCs in vitro and promotes a favorable endometrial immune profile in vivo, highlighting its potential as an immunotherapy in assisted reproduction. Full article

The inflammatory and metabolic complexity of colitis necessitates therapies that act on multiple immune pathways. Using serum proteomic profiling, the present study evaluated the systemic immunomodulatory profile of Epilobium angustifolium lyophilized methanol-aqueous extract rich in oenothein B (EAE) in a dextran sulfate sodium (DSS)-induced mouse model of ulcerative colitis in a comparative manner to dexamethasone (DXM). DSS exposure triggered robust inflammatory activation, evidenced by elevated chemokines (CXCL9, CXCL10, CCL11), proinflammatory cytokines (IL-1α, IL-12, PAI-1, RAGE) and metabolic stress mediators (leptin, resistin, FGF-21). Treatment with EAE significantly attenuated this inflammatory profile, notably reducing Th2-skewed chemokines and eosinophil recruitment. In contrast to DXM, EAE uniquely normalized pro-thrombotic and tissue-remodeling markers, including PAI-1 and RAGE, both implicated in intestinal barrier dysfunction and chronic inflammation. Furthermore, EAE demonstrated superior modulation of inflammation-associated growth factors (IGFBP-5, HGF, Flt3L) and adipokines (leptin, resistin), indicating a broader therapeutic scope that includes metabolic dysfunctions. Collectively, our data reveal that EAE exerts a distinct immunoregulatory profile, modulating both innate and adaptive immune pathways while simultaneously addressing metabolic pathologies. These multifaceted actions underscore its promise as a phytotherapeutic candidate for the management of ulcerative colitis and other inflammatory conditions, with potential advantages over conventional steroid treatment. Full article

Background: Endometriosis, believed by many to be rooted in immunology, is a chronic disease. Upregulation of programmed cell death protein 1 (PD-1) in immune cells may compromise their defensive function, a mechanism demonstrated in the context of cancer spread. This study aims to explore the potential involvement of PD-1 in the pathophysiology and progression of endometriosis. A total of 62 patients who underwent laparoscopic surgery were analyzed, with 47 diagnosed with endometriosis and 15 serving as controls. We collected peritoneal fluid and peripheral blood samples during surgery and examined them using flow cytometry. Using a panel of monoclonal antibodies, the samples were stained and the expression of PD-1 in immune cells was evaluated. Results: We observed a statistically significant rise in the percentage of the CD56⁺ CD16⁺ NK cell subset expressing PD-1 within the peritoneal fluid of endometriosis patients compared to the control group (p = 0.021). Similarly, we found that PD-1 expression on immune cells significantly differed based on factors such as body mass index and smoking habits. Moreover, peritoneal subsets of PD-1⁺ T and NK cells showed an increase in patients presenting symptomatic endometriosis and those with more widespread disease. Conclusions: Our evaluation of the inhibitory PD-1 receptor has strengthened the potential connection between immune escape mechanisms often seen in cancer cells and those in endometriotic cells. This concept could pave the way for future research in the field of immunomodulation and endometriosis. Full article

Lung cancer is the most common cause of death due to cancer in the world, and non-small cell lung cancer (NSCLC) is the most common form of lung cancer, representing approximately 84% of all cases. Due to its frequency and mortality, the amount of research on this subject has been greatly increased and new techniques to improve health outcomes have been established. While surgery remains the gold standard of treatment, immunotherapy used alone or in conjunction with surgery shows promising results. This review aims to give an overview of current and new surgical and immunotherapy methods used for the treatment of NSCLC, as well as ways in which they can be combined and the clinical outcomes for patients with each treatment modality. Additionally, it will seek to highlight any gaps in current knowledge of treatment and propose further studies to improve the efficacy of NSCLC treatments. Full article

Neutrophils are an essential protective component of the innate immune system. However, in severe bacterial infections, neutrophils are known to mis-localise from the primary site of infection to other organs, where excessive release of cytokines, chemokines, and neutrophil extracellular traps (NETs) can induce organ damage and death. In this study, we use an animal model of bacterial infection originating in the peritoneum to show that hydrogen peroxide (H₂O₂, a potent neutrophil chemoattractant) is initially released in high concentrations both in the peritoneum and in multiple ‘off-target’ organs (lungs, liver and kidneys). The initial high H₂O₂ release inhibits neutrophil chemotaxis, but after 24 h concentrations of H₂O₂ reduce and can promote neutrophil migration to organs, where they release pro-inflammatory cytokines and chemokines along with NETs. The antimalarial compound artesunate potently inhibits neutrophil migration to off-target organs. It also abolishes cytokine, chemokine, and NET production, suggesting that artesunate may be a valuable novel therapy for preventing off-target organ inflammation associated with severe bacterial infections. Finally, the potency of H₂O₂ as a chemoattractant is shown by in vitro experiments in which, faced with competing gradients of H₂O₂ and other chemoattractants, neutrophils preferentially migrate towards H₂O₂. Full article