International immunology最新文献_第8页

All-trans retinoic acid suppresses IL-4 and IL-13 production in Th2 cells by modulating the nuclear receptor RARα, and Gfi1. 全反式维甲酸通过调节核受体RARα和Gfi1抑制Th2细胞中IL-4和IL-13的产生。

IF 3.4 4区医学

International immunology Pub Date : 2025-12-24 DOI: 10.1093/intimm/dxaf040

Biswajit Biswas, Sayantee Hazra, Supratik Nandan, Shagnik Chattopadhyay, Swayam Prava Mansingh, Ritobrata Goswami

{"title":"All-trans retinoic acid suppresses IL-4 and IL-13 production in Th2 cells by modulating the nuclear receptor RARα, and Gfi1.","authors":"Biswajit Biswas, Sayantee Hazra, Supratik Nandan, Shagnik Chattopadhyay, Swayam Prava Mansingh, Ritobrata Goswami","doi":"10.1093/intimm/dxaf040","DOIUrl":"10.1093/intimm/dxaf040","url":null,"abstract":"All-trans retinoic acid (atRA), the bioactive component of vitamin A, plays a pivotal role in various biological processes. atRA, essential for embryonic development and immune functions, primarily mediates its regulatory effects by interacting with the nuclear receptor RARα (retinoic acid receptor α). atRA-bound RARα enters the nucleus and forms a heterodimer with RXR (retinoid X receptor). This heterodimer can then interact with various transcription factors to form regulatory complexes that influence gene expression. While the role of atRA in regulating the type 2 immune response has been studied, further exploration into its specific involvement in Th2 cell differentiation is necessary to fully elucidate underlying mechanisms and assess its therapeutic potential. Our study shows that atRA suppressed the Th2 phenotype by downregulating type 2 transcription factors such as Spi1 and cMaf, without altering Gata3 expression. atRA also reduced IL-4 and IL-13 production, while enhancing IL-5 expression, potentially through upregulation of Gfi1. atRA increased the Gfi1 recruitment to the Il4 and Il13 promoters, along with the common enhancer Ecr (evolutionarily conserved region). RARα, which is typically an inducer of Il4 and Il13, was observed to decrease recruitment to these loci in atRA-treated Th2 cells. Comparative gene expression analysis revealed a reduction in inflammatory responses in atRA-treated Th2 cells. Furthermore, these cells exhibited a negative correlation with epigenetic modifications and nuclear receptor activity among other biological processes. Collectively, our findings suggest that atRA can effectively suppress the Th2 phenotype in vitro, through the regulation of key type 2 transcription factors and pathways, indicating its potential therapeutic implications for limiting type 2 immune responses.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"755-771"},"PeriodicalIF":3.4,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TREX1 exonuclease in immunity and disease. TREX1外切酶在免疫和疾病中的作用。

IF 3.4 4区医学

International immunology Pub Date : 2025-12-24 DOI: 10.1093/intimm/dxaf037

Zehua Shang, Lei Wang, Wen Zhou

引用次数: 0

The thyroid hormone receptor beta (TR-β) signaling controls pathogenic Th17 cells in autoimmune disease. 甲状腺激素受体β (TR-β)信号控制自身免疫性疾病的致病性Th17细胞。

IF 3.4 4区医学

International immunology Pub Date : 2025-12-24 DOI: 10.1093/intimm/dxaf045

Yoshimitsu Doi, Ben J E Raveney, Atsuko Kimura, Manu S Mallahalli, Kimitoshi Kimura, Wakiro Sato, Shinji Oki, Takashi Yamamura

{"title":"The thyroid hormone receptor beta (TR-β) signaling controls pathogenic Th17 cells in autoimmune disease.","authors":"Yoshimitsu Doi, Ben J E Raveney, Atsuko Kimura, Manu S Mallahalli, Kimitoshi Kimura, Wakiro Sato, Shinji Oki, Takashi Yamamura","doi":"10.1093/intimm/dxaf045","DOIUrl":"10.1093/intimm/dxaf045","url":null,"abstract":"The role of the thyroid hormone receptor beta (TR-β) in the immune system remains poorly understood; although its effect on TGF-β signaling has been reported in nonimmune systems. Here, we report that Thrb is highly expressed in pathogenic CD4+ T cells that infiltrate the central nervous system during experimental autoimmune encephalomyelitis (EAE), and Thrb is exclusively expressed in IL-17-producing CD4+ T cells (Th17 cells) that develop both in vitro or in vivo. Sobetirome, a selective TR-β agonist, promoted pathogenic Th17 differentiation and IL-17 production in the presence of exogenous IL-1β. Conversely, small interfering RNA (siRNA)-mediated silencing of TR-β reduced IL-17 production, further supporting a T cell-intrinsic role of TR-β. Because C75, an inhibitor of de novo lipogenesis, blocked Th17 cell differentiation by sobetirome, the influence of TR-β signaling on Th17 cell induction is likely to act via a de novo lipogenesis-dependent mechanism. Furthermore, blocking TR-βexpression by siRNA changed the balance of IL-10/IL-17 production in cultured splenocytes, favoring an IL-10 phenotype. In contrast, IL-10 production by T cells was attenuated by activating TR-β signaling with sobetirome. Finally, the manipulation of TR-β signaling altered the severity of autoimmune disease: blocking TR-β reduced passive EAE and enhancing TR-β increased active EAE. These effects were accompanied by corresponding changes in the IL-10/IL-17 balance in encephalitogenic CD4+ T cells. In summary, our results demonstrate that TR-β signaling controls pathogenic Th cell function and autoimmunity.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"789-803"},"PeriodicalIF":3.4,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Folic acid supplementation during pregnancy alleviates food allergy in offspring by inhibiting mast cell degranulation. 怀孕期间补充叶酸可通过抑制肥大细胞脱颗粒减轻后代的食物过敏。

IF 3.4 4区医学

International immunology Pub Date : 2025-12-24 DOI: 10.1093/intimm/dxaf042

Qianwei Wang, Yuchi Jiang, Sufang Duan, Ignatius Man-Yau Szeto, Huilian Che, Changqi Liu, Xiaohui Guo

{"title":"Folic acid supplementation during pregnancy alleviates food allergy in offspring by inhibiting mast cell degranulation.","authors":"Qianwei Wang, Yuchi Jiang, Sufang Duan, Ignatius Man-Yau Szeto, Huilian Che, Changqi Liu, Xiaohui Guo","doi":"10.1093/intimm/dxaf042","DOIUrl":"10.1093/intimm/dxaf042","url":null,"abstract":"Studies have been exploring the connection between the intake of vitamins and the development of food allergy, with a particular focus on folic acid (FA). However, the impact of FA supplementation on food allergy remains a subject of debate. In the present study, the anti-allergic properties of FA and its possible mechanism of action were investigated. In a Brown Norway rat food allergy model, we found that FA downregulated the expression of specific antibodies, while influencing the Th1/Th2 balance. Furthermore, FA was found to reduce the release of particulate matter such as histamine and mast cell proteinase. Transcriptomic analysis provided evidence that FA intervention could reverse gene expression changes induced by food allergies. The gene Hsp90, responsible for producing heat shock proteins (HSP), emerged as a potential key gene involved in the process. In vitro RBL-2H3 cell-based assays suggested that FA might affect HSP90 expression through the glucocorticoid receptor (GR), leading to a reduction in effector cell degranulation. Overall, the results of this study indicate that FA has an alleviating effect on food allergies, with high doses of FA exhibiting more pronounced effects. Moreover, FA's impact on HSP90 expression through GR seems to contribute to a decrease in degranulation during the effector phase.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"773-788"},"PeriodicalIF":3.4,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Epigenomic control of immunity: from mechanisms to therapeutic targets in inflammatory bowel diseases. 免疫的表观基因组控制：从炎症性肠病的机制到治疗靶点。

IF 3.4 4区医学

International immunology Pub Date : 2025-12-24 DOI: 10.1093/intimm/dxaf039

Han-Yu Shih, Giuseppe Sciumè, Yohei Mikami

{"title":"Epigenomic control of immunity: from mechanisms to therapeutic targets in inflammatory bowel diseases.","authors":"Han-Yu Shih, Giuseppe Sciumè, Yohei Mikami","doi":"10.1093/intimm/dxaf039","DOIUrl":"10.1093/intimm/dxaf039","url":null,"abstract":"This review presents an overview of the emerging roles of epigenomic regulation in immune cell function, with a particular focus on its relevance in inflammatory bowel diseases (IBD). Epigenetic mechanisms, including DNA methylation, histone modification, chromatin remodeling, and non-coding RNAs, are essential in directing immune cell development, activation, and lineage commitment. Advances in genomics and epigenomics have highlighted the dynamic nature of gene regulation as the cornerstone of immune homeostasis and adaptability. We summarize recent insights into enhancer dynamics, three-dimensional chromatin architecture, transcription factor signaling, and microRNA (miRNA)-mediated regulation that reshape our understanding of immune-mediated diseases. These findings not only deepen our knowledge of disease pathogenesis but also offer promising targets for therapeutic intervention. In this context, miRNAs have emerged as key post-transcriptional regulators with significant diagnostic and therapeutic potential for IBD. The field of immune epigenomics is advancing rapidly, offering powerful tools for dissecting complex immune responses and guiding the development of precise therapies for chronic inflammatory conditions.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"733-742"},"PeriodicalIF":3.4,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12730870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cellular metabolism in Th9, Th17, and Treg cell differentiation. Th9， Th17和Treg细胞分化中的细胞代谢。

IF 3.4 4区医学

International immunology Pub Date : 2025-11-27 DOI: 10.1093/intimm/dxaf032

Toshio Kanno, Keiko Nakano, Yusuke Endo

{"title":"Cellular metabolism in Th9, Th17, and Treg cell differentiation.","authors":"Toshio Kanno, Keiko Nakano, Yusuke Endo","doi":"10.1093/intimm/dxaf032","DOIUrl":"10.1093/intimm/dxaf032","url":null,"abstract":"CD4+ helper T (Th) cell subsets play an essential role in the regulation of adaptive immunity. Th9, Th17, and regulatory T (Treg) cells require transforming growth factor-beta (TGF-β) for their differentiation; however, their respective functions are highly distinct. Recent studies have highlighted the critical role of cellular metabolism in initiating clonal expansion and facilitating the effector differentiation of Th cells. Upon antigen exposure, naïve CD4+ T cells undergo metabolic reprogramming to fulfill their bioenergetic and biosynthetic demands. This process involves a shift from fatty acid oxidation to glycolysis, which ensures a sufficient energy supply for activation and proliferation. Lipid metabolism plays a pivotal role in modulating the differentiation and function of Th17, Treg, and Th9 cells. This review explores the influence of metabolic pathways on key transcription factors, including retinoic-acid-related orphan receptor gamma t (RORγt) and SMADs, and emphasizes their regulatory roles in Th cell differentiation. Furthermore, it discusses emerging therapeutic strategies aimed at targeting cellular metabolism to address autoimmune and inflammatory diseases associated with these T-cell subsets.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"673-682"},"PeriodicalIF":3.4,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12658748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modulating dendritic cell function in allergic asthma with Toxoplasma gondii serine protease inhibitor 1. 刚地弓形虫丝氨酸蛋白酶抑制剂对过敏性哮喘树突状细胞功能的调节

IF 3.4 4区医学

International immunology Pub Date : 2025-11-27 DOI: 10.1093/intimm/dxaf034

Joel Katan Piñeiro, Ariadna Soledad Soto, Ana Farias, Matías Perrone Sibilia, Vanesa Roxana Sánchez, Valentina Martin, Paula Mercedes Berguer, Débora Judith Seigelshifer, Ignacio Martín Fenoy, Alejandra Goldman

{"title":"Modulating dendritic cell function in allergic asthma with Toxoplasma gondii serine protease inhibitor 1.","authors":"Joel Katan Piñeiro, Ariadna Soledad Soto, Ana Farias, Matías Perrone Sibilia, Vanesa Roxana Sánchez, Valentina Martin, Paula Mercedes Berguer, Débora Judith Seigelshifer, Ignacio Martín Fenoy, Alejandra Goldman","doi":"10.1093/intimm/dxaf034","DOIUrl":"10.1093/intimm/dxaf034","url":null,"abstract":"Tolerogenic adjuvants can enhance allergy vaccine efficacy. We previously showed that intranasal administration of recombinant Toxoplasma gondii serine protease inhibitor 1 (rTgPI-1) with ovalbumin alleviates asthma symptoms in mice. This study investigates the immunomodulatory mechanisms of rTgPI-1, focusing on its effect on dendritic cells (DCs). Bone marrow-derived DCs (BMDCs) were generated in the presence of rTgPI-1 and analyzed for their phenotype. rTgPI-1 exposed BMDCs showed reduced CD80, CD86, and MHCII, increased PDL-1 and CD45Rb, and a higher IL-10/IL-12 ratio. These BMDCs induced fewer CD69⁺CD4⁺ T cells, decreased proliferation and secretion of IL-17 and IL-4, and increased CD4⁺FoxP3⁺ T cells. In vivo, intranasal co-administration of rTgPI-1 with allergen in asthmatic mice reduced CD80high/CD86high DCs, expanded lung CD4⁺FoxP3⁺ regulatory T cells, and decreased the cDC2 subset, correlating with reduced IL-4 levels. Importantly, nafamostat mesylate-a synthetic serine protease inhibitor previously shown to alleviate asthma symptoms-failed to induce FoxP3⁺ T cells both in vitro and in vivo, underscoring the unique tolerogenic activity of rTgPI-1. Finally, stimulation of peripheral blood mononuclear cells from mite-allergic patients with house dust mite extract in the presence of rTgPI-1 led to reduced allergen-specific IL-4 and IL-5 secretion. These findings demonstrate that rTgPI-1 promotes a semimature, tolerogenic DC phenotype, suppresses T cell activation, and fosters regulatory T cell differentiation. Moreover, rTgPI-1 selectively modulates DC subsets in vivo. The observed effects on patient-derived PBMCs support its potential for further preclinical development as an adjuvant for allergen-specific immunotherapy.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"695-710"},"PeriodicalIF":3.4,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Antigen-presenting cells and lung CD8⁺ resident memory T cells coordinate local immune protection and shape responses to respiratory virus infection. 抗原提呈细胞和肺CD8 +常驻记忆T细胞协调局部免疫保护，形成呼吸道病毒感染反应。

IF 3.4 4区医学

International immunology Pub Date : 2025-11-27 DOI: 10.1093/intimm/dxaf033

Takumi Kawasaki, Moe Ikegawa, Taro Kawai

{"title":"Antigen-presenting cells and lung CD8⁺ resident memory T cells coordinate local immune protection and shape responses to respiratory virus infection.","authors":"Takumi Kawasaki, Moe Ikegawa, Taro Kawai","doi":"10.1093/intimm/dxaf033","DOIUrl":"10.1093/intimm/dxaf033","url":null,"abstract":"The respiratory mucosa, encompassing the lungs and nasal tissues, serves as the primary barrier against respiratory viruses. While neutralizing antibodies are effective at preventing viral entry, virus-specific CD8⁺ T cells play a vital role in eliminating infected cells and inducing an antiviral state, which curbs disease progression. Among these, CD8⁺ tissue-resident memory T (TRM) cells persist long-term in the lungs, where they serve as first responders and rapidly expand upon secondary respiratory virus infection to provide local protection. The establishment and maintenance of lung CD8⁺ TRM cells require not only local cytokine signals but also antigen presentation. Specific subsets of antigen-presenting cells, such as dendritic cells, alveolar macrophages, monocytes, and endothelial cells also influence the quality and durability of CD8⁺ TRM cell responses. This review summarizes key findings on CD8⁺ T-cell dynamics during respiratory viral infections, with a particular focus on CD8⁺ TRM-cell formation and function. We also highlight the importance of local antigen presentation in driving TRM development and discuss how this knowledge can inform vaccine strategies aimed at eliciting robust, long-lasting mucosal immunity.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"663-672"},"PeriodicalIF":3.4,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The impact of Talin2, a signaling protein regulating the focal adhesion complex, on asthma. Talin2（一种调节局灶黏附复合物的信号蛋白）对哮喘的影响。

IF 3.4 4区医学

International immunology Pub Date : 2025-11-27 DOI: 10.1093/intimm/dxaf026

DaYeon Hwang, Min-Hyeok An, Pureun-Haneul Lee, SangMin Yoon, Yunha Nam, Shinhee Park, Ae-Rin Baek, An-Soo Jang

{"title":"The impact of Talin2, a signaling protein regulating the focal adhesion complex, on asthma.","authors":"DaYeon Hwang, Min-Hyeok An, Pureun-Haneul Lee, SangMin Yoon, Yunha Nam, Shinhee Park, Ae-Rin Baek, An-Soo Jang","doi":"10.1093/intimm/dxaf026","DOIUrl":"10.1093/intimm/dxaf026","url":null,"abstract":"Talin protein as a mechanosensitive cytoskeleton protein connects the extracellular matrix to the cytoskeleton by linking to integrins and actin, thereby mediating the conversion of mechanical signals into biochemical signals and influencing disease progression. The biological significance of Talin2 in asthma is not well understood. The aim of this study was to elucidate the role of Talin2 in asthma. Mice sensitized and challenged with ovalbumin (OVA) or saline and MRC-5 cells were used to investigate the role of Talin2 in the pathogenesis of bronchial asthma. In addition, Talin2 levels were measured in the plasma of control subjects and asthmatic patients. The relationships between Talin2 and clinical variables in asthmatic patients were also examined. Plasma Talin2 levels were higher in asthmatic patients than control subjects. In asthmatic patients, Talin2 levels correlated with FEV1 % pred., FVC % pred., and FEV1/FVC, and the blood neutrophils and lymphocyte proportion. The receiver operating characteristic curves for Talin2 levels differed between control subjects and asthmatic patients. Talin2, Kindlin2, Integrin β1 and F-actin levels were significantly increased in MRC-5 cells exposed to Der p 1, but decreased in MRC-5 cells treated with talin2 siRNA. The BALF and serum levels of cytokines (IL-4, IL-5, and TNF-α) were elevated in OVA mice compared to the control mice. Talin2, Kindlin2, Integrin β1, and F-actin protein expression in lung tissue was significantly higher in OVA mice than control mice. These results suggest that Talin2 be involved in the pathogenesis of asthma, and may be a marker for asthma.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"683-694"},"PeriodicalIF":3.4,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Interleukin-35 regulates the differentiation of regulatory T cells through the JAK-STAT pathway and influences glutamine metabolism in ARDS. 白细胞介素-35通过JAK-STAT通路调控调节性T细胞的分化，影响ARDS患者谷氨酰胺代谢。

IF 3.4 4区医学

International immunology Pub Date : 2025-11-27 DOI: 10.1093/intimm/dxaf041

Qiao-Zhi Peng, Mu Zhang, Ai-Pin Zhang, Min-Kang Guo, Ren-Jie Luo, Ling Zeng, Chang Chen, Shi-Hui Lin, Fang Xu, Ke Xie

{"title":"Interleukin-35 regulates the differentiation of regulatory T cells through the JAK-STAT pathway and influences glutamine metabolism in ARDS.","authors":"Qiao-Zhi Peng, Mu Zhang, Ai-Pin Zhang, Min-Kang Guo, Ren-Jie Luo, Ling Zeng, Chang Chen, Shi-Hui Lin, Fang Xu, Ke Xie","doi":"10.1093/intimm/dxaf041","DOIUrl":"10.1093/intimm/dxaf041","url":null,"abstract":"The aim of this study was to elucidate the effect of interleukin (IL)-35 on T-cell differentiation and its mechanism. We evaluated the therapeutic effect of IL-35 on acute respiratory distress syndrome using clinical samples and the mouse cecum ligation and puncture model. The effects of IL-35 on regulatory T cells (Tregs) were verified by flow cytometry, immunohistochemistry, and quantitative real-time reverse transcription polymerase chain reaction. Liquid chromatography-mass spectrometry was used to detect the effects of IL-35 on changes in glutamine metabolites and tricarboxylic acid (TCA) circulation. Western blot was used to detect changes in forkhead box protein 3 (Foxp3), key enzymes, and signal transducer and activator of transcription (STAT) phosphorylation subgroup proteins in the presence of cerdulatinib. Finally, A549 cells were treated with EL-4 cell supernatant to explore the effect of cerdulatinib on the therapeutic effect of IL-35 injury. Inflammatory factors decreased, and Foxp3 increased in response to IL-35. In addition, Foxp3 was upregulated in a glutamine-deficient environment, and notably, glutamine-related metabolism and TCA cycle-related substances were altered with the involvement of IL-35. IL-35 upregulated phosphorylation of STAT isoforms, and cerdulatinib reversed it. Finally, the effects of IL-35 on Foxp3, key enzymes, and glutamine metabolite changes were all reversed by cerdulatinib. Our study shows that IL-35 reduces lung inflammation and promotes Treg differentiation. IL-35 affects the glutamine metabolism and the TCA cycle. In addition, we demonstrated that the relevant functions of IL-35 may be mediated by STAT isoform phosphorylation.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"711-727"},"PeriodicalIF":3.4,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0