Cytokine最新文献

{"title":"FcRn inhibitors in immune thrombocytopenia: A comprehensive review of therapeutic advances and clinical outcomes","authors":"Mohammad Ali Nilforoushzadeh ,&nbsp;Nazila Heidari ,&nbsp;Seyedayin Hosseini ,&nbsp;Negar Ghotbi ,&nbsp;Mahdi Abdollahi Namanloo ,&nbsp;Amirhossein Heidari","doi":"10.1016/j.cyto.2025.156971","DOIUrl":"10.1016/j.cyto.2025.156971","url":null,"abstract":"<div><div>Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet counts, leading to bleeding risks. Despite existing treatments, many patients with chronic or refractory ITP remain inadequately managed. Fc-receptors, including neonatal Fc receptor (FcRn), play a crucial role in the ITP pathogenesis by activating antibody-dependent cell-mediated cytotoxicity and antibody-dependent cell-mediated phagocytosis, leading to platelet destruction. In addition, recent insights highlight cytokine dysregulation, particularly involving interleukin (IL)-17, IL-6, and Interferon-gamma (IFN-γ), as contributing to disease persistence and immune dysfunction. We sought to evaluate the efficacy and safety of FcRn inhibitors for chronic or persistent ITP treatment. PubMed/Medline, Scopus, and Web of Science databases were systematically searched until January 16th, 2025. Preclinical and clinical studies with available full-text in English were included. Efgartigimod significantly improved platelet counts and reduced Immunoglobulin G (IgG) levels in refractory as well as chronic patients with minimal adverse effects. Rozanolixizumab also showed favorable outcomes in terms of platelet count elevation and IgG reduction in Phase 2 and Phase 3 clinical trials in cases who were unresponsive to ≥2 standard-of-care ITP treatments. These immunotherapeutic agents can effectively increase platelet counts and reduce IgG serum levels, addressing a critical need in patients who do not respond to corticosteroids, thrombopoietin receptor agonists (TPO-RAs), and rituximab. Further long-term studies are warranted to confirm these findings and explore their broader clinical implications.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"193 ","pages":"Article 156971"},"PeriodicalIF":3.7,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144254213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoplasmic reticulum stress markers in tularemia: a case-control study","authors":"Yasemin Çakır Kıymaz ,&nbsp;Serkan Bolat","doi":"10.1016/j.cyto.2025.156977","DOIUrl":"10.1016/j.cyto.2025.156977","url":null,"abstract":"<div><div>Tularemia is a zoonotic infectious disease caused by <em>Francisella tularensis</em>. It is transmitted by rodents and results in an infectious disease characterized by lymphadenopathy. This study aims to evaluate the role of endoplasmic reticulum (ER) stress in patients with tularemia. This prospective, case-control study was conducted between June and August 2024 at the Infectious Diseases and Clinical Microbiology Clinics of Sivas Cumhuriyet University Hospital, Sivas, Turkey. The study included 40 patients aged 18 years and older diagnosed with tularemia. The control group comprised 30 healthy individuals. The serum levels of ER stress markers (EIF2α, GRP78, and CHOP) were compared between patients and control groups. The mean age of the patients was 44 ± 16 years, and 72.5 % (<em>n</em> = 29) were female. The control group had a mean age of 37 ± 12 years, and 36 % (<em>n</em> = 11) were female. The most common clinical form of tularemia was oropharyngeal (82.5 %, <em>n</em> = 33). Levels of EIF2α, GRP78, and CHOP were significantly higher in the tularemia patient group compared to the control group (<em>p</em> &lt; 0.001). Although ER stress protein levels were higher in patients who did not require lymph node dissection than in those who did, the difference was not statistically significant. Additionally, no significant difference was observed in ER stress protein levels between patients who responded to treatment and those who did not. The results of this study indicate that ER stress molecules such as CHOP, EIF2α, and GRP78 exhibit significant increases during tularemia infection. These data support the role of the ER stress pathway in the pathogenesis of tularemia.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"193 ","pages":"Article 156977"},"PeriodicalIF":3.7,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144254222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of Progranulin and its related mechanism with exosomes from peripheral blood mononuclear cells CD4 + T cells in patients with thyroid-associated ophthalmopathy","authors":"Lina Wang ,&nbsp;Yue Hai ,&nbsp;Xueying Zeng ,&nbsp;Yaling Peng ,&nbsp;Mengfei Wang ,&nbsp;Tong Wu","doi":"10.1016/j.cyto.2025.156962","DOIUrl":"10.1016/j.cyto.2025.156962","url":null,"abstract":"<div><div>Background: The expression of serum progranulin (PGRN) and the related immunological mechanisms of peripheral blood mononuclear cells (PBMCs) CD4 + T cells exosomes in thyroid-associated ophthalmopathy (TAO) are currently hot topics of research. Material and Method: A total of 27 patients with active TAO and 59 healthy individuals were included in the study for comparison. PBMCs were isolated from the patients' blood, and naïve CD4+ T cells were purified using human naïve CD4 microbeads. One co-culture group was not supplemented with PGRN, serving as the PGRN-untreated group (AG), while another group was supplemented with extracted PGRN, serving as the PGRN-treated group (BG). CD4+ T cells derived from the blood of healthy individuals were used as the control group (CG). Result: The serum PGRN concentration in TAO patients was visibly higher as against the CG; The contents of interleukin (IL-10), IL-4, and IL-17 in BG were visibly lower as against AG; The protein and mRNA expression of cytokines in BG were visibly lower as against AG; The proliferation level of CD4 + T cells was visibly lower, and the apoptosis level was visibly higher in BG as against AG (<em>P</em> <em>&lt;</em> 0.05). Conclusion: PGRN may be implicated in the pathogenesis of TAO. It could modulate the immune response by reducing cytokine release in CD4+ T cell-derived exosomes, inhibiting the proliferation of CD4+ T cells, and promoting their apoptosis.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"193 ","pages":"Article 156962"},"PeriodicalIF":3.7,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GABA and GABAergic dysfunction in COVID-19: Piecing the puzzle with targeting immunity and several inflammatory pathways","authors":"Hamza M.A. Eid ,&nbsp;Hayder M. Al-Kuraishy ,&nbsp;Ali I. Al-Gareeb ,&nbsp;Mohamed N. Fawzy ,&nbsp;Marios Papadakis ,&nbsp;Yahya A. Almutawif ,&nbsp;Athanasios Alexiou ,&nbsp;Gaber El-Saber Batiha","doi":"10.1016/j.cyto.2025.156976","DOIUrl":"10.1016/j.cyto.2025.156976","url":null,"abstract":"<div><div>Coronavirus disease 2019 (COVID-19) is a global pandemic disease caused by a new type of respiratory virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The primary factors contributing to inflammatory and immunological diseases in patients with severe COVID-19 are primarily attributed to the excessive activation of T cells and macrophages, resulting in the massive release of pro-inflammatory cytokines, including interleukins and chemokines. Studies have indicated that the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) possesses anti-inflammatory properties in mitigating certain inflammatory disorders. It has been shown that inflammation and oxidative stress caused by COVID-19 infection may lead to a disruption of GABAergic neurotransmission in COVID-19 patients. GABA and GABA agonists could be potential successful treatments for the management of COVID-19 by inhibiting the release of pro-inflammatory cytokines and inflammatory pathways such as nuclear factor kappa B (NF-κB) and the nod-like receptor pyrin 3 (NLRP3) inflammasome. Therefore, the purpose of this review was to discuss the potential role of GABA and GABA agonists in the alleviation of inflammatory disorders caused by COVID-19.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"193 ","pages":"Article 156976"},"PeriodicalIF":3.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144194680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated CXCL1 expression contributes to the development of pediatric Crohn's disease and serves as a diagnostic marker: A reanalysis based on the integrative bioinformatics","authors":"Xiaohong Xu,&nbsp;Jie Wu","doi":"10.1016/j.cyto.2025.156972","DOIUrl":"10.1016/j.cyto.2025.156972","url":null,"abstract":"<div><h3>Purpose</h3><div>Pediatric Crohn's disease (PCD), which is a severe illness impacting the physical health of children. Nevertheless, there is still a lack of highly efficient diagnostic markers. Here, we aim to develop efficient diagnostic and treatment approaches, gaining a deeper understanding of the molecular mechanisms and potential targets causing PCD.</div></div><div><h3>Methods</h3><div>PCD datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between PCD and normal were screened by Limma package. DEGs were subjected to further analyses utilizing GO, KEGG, GSEA and PPI analysis. The CIBERSORT analysis aimed at examining the correlation between CXCL1 and immune infiltration. The clinical diagnostic value of CXCL1 and drugs targeting CXCL1 were analyzed through ROC and CMap database. Additionally, intestinal mucosal tissue samples from PCD patients were collected to conduct qRT-PCR for detecting the expression of CXCL1.</div></div><div><h3>Results</h3><div>Overall, 71 DEGs were selected from GSE101794 and GSE93624. A total of 15 hub genes were identified by the constructed PPI network, among which CXCL1 was significantly increased in intestinal tissue in the PCD patients. DEGs between high- and low-CXCL1 expression were mainly enriched in the IL-17 and NF-kappa B signaling pathways. ROC analysis showed that AUC values of CXCL1 were 0.908, 0.945 and 0.890 based on GSE101794, GSE93624 and GSE57945, the similar results was obtained using qRT-PCR. The immune infiltration results indicate that CXCL1 could potentially play a regulatory role in the immune response of PCD.</div></div><div><h3>Conclusions</h3><div>We have determined that CXCL1 might have a crucial involvement in the advancement of PCD, thus having the potential to be a diagnostic marker in order to enhance treatment choices for PCD.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"192 ","pages":"Article 156972"},"PeriodicalIF":3.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144189607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A cross-sectional study investigating the underlying inflammatory mechanisms of post-stroke insomnia","authors":"Lang Zhao ,&nbsp;Ting Sun ,&nbsp;Ping Tong,&nbsp;Lu Yang,&nbsp;Yuan-Hong Shi","doi":"10.1016/j.cyto.2025.156975","DOIUrl":"10.1016/j.cyto.2025.156975","url":null,"abstract":"<div><h3>Background</h3><div>It is widely postulated that inflammation contributes to the pathogenesis of both stroke and insomnia; and vice versa. However, the mechanism underlying post-stroke insomnia (PSI) remains ambiguous. Therefore, this study aims to elucidate the potential inflammatory mechanisms associated with PSI and evaluate its predictive value.</div></div><div><h3>Methods</h3><div>A cross-sectional study was conducted among patients with acute stroke who were enrolled in this investigation. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI), alongside the assessment of 12 cytokines and complement component 1q (C1q) levels. The anxiety (HAD-A) and depression (HAD-D) states of patients were assessed utilizing the Hospital Anxiety and Depression Scale. Statistical analyses were conducted to compare differences in each indicator among patients with various types of stroke and varying sleep quality.</div></div><div><h3>Results</h3><div>The prevalence of sleep disorders among patients with acute stroke is as high as 75.7 %. There were no significant differences observed in the PSQI scores and cytokines across different subtypes of strokes. However, significant differences were found in Interleukin (IL)-6, Interferon-α(IFN-α), and C1q levels, as well as in HAD-A and HAD-D scores among PSI patients. Binary logistic regression analysis revealed that C1q, IL-6, IL-10, IL-12, HAD-A, and HAD-D had a significant impact on sleep quality. The receiver operating characteristic (ROC) curve indicated that only IL-6 and HAD-A scores predicted PSI.</div></div><div><h3>Conlusion</h3><div>Insomnia is common after acute stroke, potentially due to inflammation. IL-6 levels and anxiety could serve as predictors for PSI development, thereby presenting potential targets for therapeutic intervention.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"192 ","pages":"Article 156975"},"PeriodicalIF":3.7,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144185030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin-enhanced CAR-engineered immune cells in tumor immunotherapy: current insights and future perspectives","authors":"Min Wang ,&nbsp;Zixuan Wang ,&nbsp;Guangji Zhang ,&nbsp;Jia Fan","doi":"10.1016/j.cyto.2025.156973","DOIUrl":"10.1016/j.cyto.2025.156973","url":null,"abstract":"<div><div>Despite the remarkable clinical success of chimeric antigen receptor (CAR)-T cell therapy in hematologic malignancies, the therapeutic efficacy of conventional second-generation CAR-T cells in treating solid tumors remains suboptimal, primarily due to three major biological barriers: (1) the immunosuppressive tumor microenvironment (TME), (2) inadequate tumor infiltration capacity, and (3) T cell exhaustion mechanisms. To overcome these limitations, innovative fourth-generation “armored” CAR-T cell platforms have been engineered with integrated cytokine-secreting modules designed to potentiate anti-tumor responses through localized immunomodulation. These advanced cellular therapeutics achieve targeted delivery of various immunostimulatory cytokines directly within the TME, thereby orchestrating three critical therapeutic effects: (I) remodeling of the immunosuppressive niche, (II) enhancement of immune cell persistence, and (III) neutralization of immunosuppressive signaling networks. This comprehensive review systematically examines the translational applications of cytokine-secreting CAR-engineered immune cells, including CAR-T, CAR-NK, and CAR-iNKT cell platforms, in solid tumor immunotherapy, with particular emphasis on multiple classes of immunomodulatory cytokines that enhance cytotoxic potential, promote immune cell survival, and counteract TME-mediated immunosuppression. We critically evaluate preclinical and clinical evidence demonstrating the therapeutic efficacy of cytokine-armed CAR-engineered cells across various tumor models, including hematological malignancies, glioblastoma, and neuroblastoma. Furthermore, this review addresses current translational challenges, particularly cytokine-associated toxicity profiles and innovative strategies for achieving spatiotemporal control of cytokine release, while discussing their potential implications for advancing clinical outcomes in solid tumor immunotherapy.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"192 ","pages":"Article 156973"},"PeriodicalIF":3.7,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive review: neuroinflammation and immune communication between the central nervous system and the periphery","authors":"Ramandeep Kaur ,&nbsp;Satish Kumar ,&nbsp;Lakhwinder Singh","doi":"10.1016/j.cyto.2025.156974","DOIUrl":"10.1016/j.cyto.2025.156974","url":null,"abstract":"<div><div>Immunity in the central nervous system (CNS) is generally attributed to neuron-associated microglia in the parenchyma. Microglial cells are specialized macrophages that interact closely with neurons to monitor them for signs of infection or injury. In addition to microglia, several other specialized macrophage populations are located at the borders of the CNS, including dural, leptomeningeal, perivascular, and choroid plexus macrophages. Collectively, these are CNS-associated macrophages (CAMs), but how these cells maintain the balance between the segregation of the CNS and the information transfer between the CNS parenchyma and the peripheral system is not well understood. The interaction between the immune system and the CNS is a newly emerging field of study that focuses on the functions of resident microglia and specialized macrophages, including leptomeningeal, choroid plexus, and perivascular macrophages. This review will help to improve understanding of the regulatory mechanisms of microglia and specialized macrophages and their involvement in the communication with the peripheral immune system. It could also advance neurological disease therapies that selectively target specific immune function parameters more effectively for managing neurodegenerative diseases.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"192 ","pages":"Article 156974"},"PeriodicalIF":3.7,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144177690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Etanercept, a peripherally restricted TNF inhibitor, enhances cocaine-induced locomotor behaviors in male, but not female, rats","authors":"Scott D. Dunn ,&nbsp;Sonita Wiah ,&nbsp;Anwar Lami ,&nbsp;Scott M. Rawls","doi":"10.1016/j.cyto.2025.156967","DOIUrl":"10.1016/j.cyto.2025.156967","url":null,"abstract":"<div><div>Cocaine dysregulates tumor necrosis factor (TNF) signaling in mesolimbic substrates, suggesting a role for TNF in cocaine-induced hyperlocomotion, a signature preclinical effect of cocaine. Inhibition of TNF signaling by genetic deletion or with a brain-penetrable TNF antagonist enhances cocaine-induced hyperlocomotion in male mice, but roles for sex and peripheral TNF are unclear. Also unknown is how peripherally restricted etanercept, the world's most widely prescribed TNF inhibitor, affects cocaine-induced locomotor responses. We determined effects of etanercept on a triad of cocaine-induced locomotor responses (e.g.<em>,</em> ambulation, stereotypy, distance traveled) in male and female rats and impacts of etanercept-cocaine exposure on tyrosine hydroxylase (TH) and dopamine transporter (DAT) mRNA levels in the ventral tegmental area (VTA). Etanercept (20 mg/kg, IP) and a submaximal dose of cocaine (10 mg/kg, IP) were used initially, and etanercept was injected 48 h before cocaine to capture peak plasma concentrations. Etanercept itself did not affect spontaneous locomotor responses in male or female rats. In male rats, etanercept increased cocaine-induced ambulatory and stereotypical activities and enhanced cocaine-induced distance traveled. Etanercept modestly reduced TH mRNA levels in the VTA of cocaine-naïve and cocaine treated male rats. Locomotor responses in male rats that were evoked by a higher dose of cocaine (20 mg/kg, IP) were not affected by etanercept. In female rats, etanercept did not affect any cocaine-induced locomotor responses. These results show that etanercept exerts effects on locomotor behaviors induced by cocaine that depend on both sex and cocaine dose and suggest that peripheral inhibition of TNF influences cocaine-induced behaviors. <strong>Key words:</strong></div><div>etanercept; TNF; cocaine; dopamine; tyrosine hydroxylase; DAT; locomotor.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"192 ","pages":"Article 156967"},"PeriodicalIF":3.7,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of IL-39 in autoimmune diseases: From general to immunopathogenesis","authors":"Parisa Ahmadi ,&nbsp;Atousa Janzadeh ,&nbsp;Maryam Honardoost ,&nbsp;Soroush Taherkhani ,&nbsp;David Doyle ,&nbsp;Negin Mojarad","doi":"10.1016/j.cyto.2025.156969","DOIUrl":"10.1016/j.cyto.2025.156969","url":null,"abstract":"<div><div>IL-39, a cytokine from the IL-12 family that appears to be produced primarily by B cells, consists of the IL-23p19 and Ebi3 subunits, which signal through IL-23R/gp130 to activate STAT1/STAT3. Some studies suggest elevated IL-39 levels in certain autoimmune conditions, such as relapsing-remitting multiple sclerosis (RRMS), ankylosing spondylitis (AS), and autoimmune thyroid disease (ATD), possibly indicating a link between IL-39 and autoimmunity mediated by B cells. Preliminary evidence indicates that IL-39 might stimulate NETosis in neutrophils and promote BAFF (B-cell activating factor) secretion, which theoretically, in turn, may activate IL-39 production, T-cell-independent IgA isotype switching and somatic hypermutation. Some reports have revealed correlations between IL-39 and disease-specific autoantibodies, including RF and ACPAs in rheumatoid arthritis (RA), anti-dsDNA in systemic lupus erythematosus (SLE), and anti-AQP4 antibodies in neuromyelitis optica spectrum disorder (NMOSD), although these associations require further confirmation. Theoretically, through NETosis, IL-39 could potentially expose intracellular antigens and facilitate their citrullination via peptidyl arginine deiminase (PAD), which might contribute to autoimmunity initiation. Some data suggest that in <em>P. gingivalis</em>-associated dysbiosis, IL-36γ may increase IL-39 secretion by epithelial cells. As dysbiosis and inflammatory bowel disease (IBD) increase gut permeability and LPS exposure—a possible stimulus for IL-39 production—the relationships among IL-39, gut dysbiosis, and autoimmunity appear to warrant further investigation. While some studies have reported conflicting results regarding the immunological activity of IL-39 in humans, these theoretical considerations suggest the need for more rigorous, standardized research, as current investigations remain limited by small sample sizes and heavy reliance on animal models or in vitro studies rather than comprehensive human studies examining the biological effects of IL-39.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"192 ","pages":"Article 156969"},"PeriodicalIF":3.7,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}