International immunology最新文献_第4页

Single-cell multiomic analysis revealed the differentiation, localization, and heterogeneity of IL10+ Foxp3- follicular T cells in humans. 单细胞多组学分析揭示了人体内IL10+ Foxp3-滤泡T细胞的分化、定位和异质性。

IF 4.8 4区医学

International immunology Pub Date : 2025-07-22 DOI: 10.1093/intimm/dxaf014

Shusei Fujioka, Mayu Fujioka, Yusuke Imoto, Yasuyo Harada, Hiroyuki Yoshitomi, Masato Kubo, Yasuaki Hiraoka, Hideki Ueno

{"title":"Single-cell multiomic analysis revealed the differentiation, localization, and heterogeneity of IL10+ Foxp3- follicular T cells in humans.","authors":"Shusei Fujioka, Mayu Fujioka, Yusuke Imoto, Yasuyo Harada, Hiroyuki Yoshitomi, Masato Kubo, Yasuaki Hiraoka, Hideki Ueno","doi":"10.1093/intimm/dxaf014","DOIUrl":"10.1093/intimm/dxaf014","url":null,"abstract":"Germinal center (GC) reactions are tightly regulated to generate high-affinity antibodies. Although IL10+ Foxp3- follicular T cells have recently been described as contributing to the suppression of GC reactions, their differentiation, localization, and heterogeneity remain incompletely understood. Additionally, it remains unclear whether IL10+ Foxp3- follicular T cells represent a transient status or an independent subset. To address these gaps, we performed integrative single-cell analysis of transcriptomes, epigenomes, surface proteomes, and TCR repertoires in human tonsillar CD4+ T cells. Unbiased clustering revealed IL10+ Foxp3- follicular T cells as a transcriptionally and epigenetically unique subset. This subset exhibited features of both T follicular helper (Tfh) and T regulatory type 1 (Tr1) cells, and accordingly, hereafter, we call them T follicular regulatory type 1 (Tfr1) cells. Analysis using imaging mass cytometry and spatial RNA-TCR sequencing demonstrated their presence within GCs in humans. Bioinformatic analysis suggested that Tfr1 cells differentiate from GC-Tfh cells upon strong TCR stimulation, a finding corroborated by mouse in vivo experiments and time-series single-cell RNA-TCR sequencing of human in vivo CD4+ T cells. Of note, our bioinformatic analysis suggested that Tfr1 cells receive strong TCR signals from ICOS-Lhigh GC-B cells, likely representing high-affinity GC-B cells. Finally, we show that Tfr1 cells acquire a resident memory phenotype following an effector phase. Together, our findings suggest that high-affinity ICOS-Lhigh GC-B cells transform follicular T cells from GC-Tfh cells to Tfr1 cells, which likely become memory cells and reside in the lymphoid organ to support effective antibody production.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"475-491"},"PeriodicalIF":4.8,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673881","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 4.8 4区医学

International immunology Pub Date : 2025-07-11 DOI: 10.1093/intimm/dxaf041

Qiao-Zhi Peng, Mu Zhang, Ai-Ping 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-Ping Zhang, Min-Kang Guo, Ren-Jie Luo, Ling Zeng, Chang Chen, Shi-Hui Lin, Fang Xu, Ke Xie","doi":"10.1093/intimm/dxaf041","DOIUrl":"https://doi.org/10.1093/intimm/dxaf041","url":null,"abstract":"The aim of this study was to elucidate the effect of IL-35 on T cell differentiation and its mechanism. We evaluated the therapeutic effect of IL-35 on acute respiratory distress syndrome (ARDS) using clinical samples and mouse cecum ligation and puncture (CLP) model. The effects of IL-35 on Regulatory T cells (Treg) were verified by flow cytometry, immunohistochemistry (IHC) and qRT-PCR. Liquid chromatography-mass spectrometry (LC-MS) was used to detect the effects of IL-35 on changes in glutamin metabolites and TCA circulation. Western blot was used to detect changes in forkhead box protein 3 (Foxp3), key enzymes and 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":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-11","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

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

IF 4.8 4区医学

International immunology Pub Date : 2025-07-08 DOI: 10.1093/intimm/dxaf037

Zehua Shang, Lei Wang, Wen Zhou

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 4.8 4区医学

International immunology Pub Date : 2025-07-08 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":"https://doi.org/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 disease (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":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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 4.8 4区医学

International immunology Pub Date : 2025-07-02 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":"https://doi.org/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. atRA-bound RARα enters the nucleus and forms a heterodimer with RXR. 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 Th2 phenotype by down-regulating 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 up-regulation of Gfi1. atRA increased the Gfi1 recruitment to the Il4 and Il13 promoters, along with the common enhancer Ecr. 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":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-02","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

Fecal Microbiota Transplantation for Immune Regulation: Improving Ulcerative Colitis and Enhancing Cancer Immunotherapy. 粪便微生物群移植用于免疫调节：改善溃疡性结肠炎和增强癌症免疫治疗。

IF 4.8 4区医学

International immunology Pub Date : 2025-07-02 DOI: 10.1093/intimm/dxaf038

Xiaochen Zhang, Dai Ishikawa, Akihito Nagahara

{"title":"Fecal Microbiota Transplantation for Immune Regulation: Improving Ulcerative Colitis and Enhancing Cancer Immunotherapy.","authors":"Xiaochen Zhang, Dai Ishikawa, Akihito Nagahara","doi":"10.1093/intimm/dxaf038","DOIUrl":"https://doi.org/10.1093/intimm/dxaf038","url":null,"abstract":"The gut microbiota plays an integral role in maintaining health and regulating various host functions, including immune responses. Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic approach to restore gut microbial balance. Although widely recognized for its efficacy in treating ulcerative colitis (UC), FMT is now being investigated as an adjuvant therapy to enhance the efficacy of immune checkpoint inhibitors (ICIs) in cancer treatment. This review summarizes the clinical applications of FMT in UC treatment and its potential role in cancer immunotherapy. FMT exhibits varying degrees of efficacy in the treatment of UC, with differences in outcomes attributed to variations in administration methods and donor selection. In cancer therapy, FMT has demonstrated the potential to improve ICI responses, particularly in patients with melanoma. However, its effects on other cancers remain unclear. Although FMT holds promise for UC and cancer immunotherapy, challenges such as inconsistent clinical outcomes and methodological variations persist. Standardized protocols and mechanistic studies are crucial to optimize FMT-based therapeutic strategies, and further research is required to establish its efficacy under diverse clinical conditions.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540112","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

Roles of fibroblasts in the pathogenesis of inflammatory bowel diseases and IBD-associated fibrosis. 成纤维细胞在炎症性肠病（ibd）发病机制和ibd相关纤维化中的作用

IF 4.8 4区医学

International immunology Pub Date : 2025-06-17 DOI: 10.1093/intimm/dxaf015

Takayoshi Ito, Hisako Kayama

{"title":"Roles of fibroblasts in the pathogenesis of inflammatory bowel diseases and IBD-associated fibrosis.","authors":"Takayoshi Ito, Hisako Kayama","doi":"10.1093/intimm/dxaf015","DOIUrl":"10.1093/intimm/dxaf015","url":null,"abstract":"Ulcerative colitis and Crohn's disease, the principal forms of inflammatory bowel disease (IBD), are chronic relapsing inflammatory disorders of the gastrointestinal tract. The incidence and prevalence of IBD have been increasing worldwide, but their etiology remains largely unknown. Although anti-TNF agents can be highly effective in IBD patients, 10%-40% of patients do not respond to primary anti-TNF therapy. Furthermore, anti-TNF therapy for IBD does not prevent the incidence and progression of fibrosis. A growing body of evidence suggests that IBD pathogenesis is associated with epithelial barrier dysfunction, inappropriate immune responses to luminal microorganisms, and environmental factors as well as host genetics. Recently, a variety of mesenchymal stromal cell populations, including fibroblasts and myofibroblasts, have been characterized in individual tissues under homeostatic and inflammatory conditions. The compositions of fibroblasts and myofibroblasts are altered in the intestinal mucosa of IBD patients, and diverse properties of these cells, such as the production of pro-inflammatory cytokines and extracellular matrix components, are remodeled. Several studies have demonstrated that IBD-specific fibroblasts are involved in anti-TNF therapy refractoriness. Therefore, a better understanding of the interaction among fibroblasts, epithelial cells, immune cells, and microbes associated with the maintenance and perturbation of intestinal homeostasis may facilitate the identification of novel therapeutic targets for IBD. This review presents the key findings obtained to date regarding the pathological and homeostatic mechanisms by which functionally distinct fibroblasts and myofibroblasts regulate epithelial barrier integrity, immunity, and tissue regeneration in health and in gastrointestinal disorders.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"377-392"},"PeriodicalIF":4.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663352","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

Neural signaling in immunology: the gateway reflex. 免疫学中的神经信号：通道反射。

IF 4.8 4区医学

International immunology Pub Date : 2025-06-17 DOI: 10.1093/intimm/dxaf009

Rie Hasebe, Hiroki Tanaka, Takeshi Yamasaki, Kaoru Murakami, Masaaki Murakami

{"title":"Neural signaling in immunology: the gateway reflex.","authors":"Rie Hasebe, Hiroki Tanaka, Takeshi Yamasaki, Kaoru Murakami, Masaaki Murakami","doi":"10.1093/intimm/dxaf009","DOIUrl":"10.1093/intimm/dxaf009","url":null,"abstract":"Neural signaling regulates various reactions in our body including immune responses. Neuromodulation of this signaling using artificial neural activation and/or suppression is a potential treatment for diseases and disorders. We here review neural signaling regulating the immune system, with a special focus on the gateway reflex. The gateway reflex is a novel neuro-immune crosstalk mechanism that regulates tissue-specific inflammatory diseases. We have discovered six gateway reflexes so far; all are induced by environmental or artificial stimulations including gravity, electrical stimulation, pain sensation, stress, light, and inflammation in joints. In the presence of increased autoreactive T cells in the blood, such stimulation activates specific neural signaling to release noradrenaline (NA) from the nerve endings at specific blood vessels in the central nervous system. NA activates the interleukin-6 (IL-6) amplifier, which leads to the hyper-activation of nuclear factor-kappa B (NF-κB) in non-immune cells, resulting in the formation of a gateway. This gateway allows autoreactive T cells and other immune cells to accumulate in the target tissue to induce inflammatory diseases. In gateway reflexes induced by stress or remote inflammation, adenosine triphosphate (ATP) secreted from inflammation sites activates specific neural pathways, resulting in organ dysfunction and inflammation in other tissues, suggesting that the gateway reflex regulates tissue-specific inflammatory diseases by bidirectional crosstalk between the neural and immune systems. We also discuss other cases of neural signaling including the inflammatory reflex.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"369-377"},"PeriodicalIF":4.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742803","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

Effect of prevaccination blood and T-cell phenotypes on antibody responses to a COVID-19 mRNA vaccine. 接种前血液和t细胞表型对COVID-19 mRNA疫苗抗体应答的影响

IF 4.8 4区医学

International immunology Pub Date : 2025-06-17 DOI: 10.1093/intimm/dxaf013

Yu Hidaka, Norihide Jo, Osamu Kikuchi, Masaru Fukahori, Takeshi Sawada, Yutaka Shimazu, Masaki Yamamoto, Kohei Kometani, Miki Nagao, Takako E Nakajima, Manabu Muto, Satoshi Morita, Yoko Hamazaki

{"title":"Effect of prevaccination blood and T-cell phenotypes on antibody responses to a COVID-19 mRNA vaccine.","authors":"Yu Hidaka, Norihide Jo, Osamu Kikuchi, Masaru Fukahori, Takeshi Sawada, Yutaka Shimazu, Masaki Yamamoto, Kohei Kometani, Miki Nagao, Takako E Nakajima, Manabu Muto, Satoshi Morita, Yoko Hamazaki","doi":"10.1093/intimm/dxaf013","DOIUrl":"10.1093/intimm/dxaf013","url":null,"abstract":"Despite the high effectiveness of the coronavirus disease 2019 (COVID-19) mRNA vaccines, both immunogenicity and reactogenicity show substantial interindividual variability. One key challenge is predicting high and low responders using easily measurable parameters. In this study, we performed multivariate linear regression analysis, which allows adjustment for confounding, to explore independent predictive factors for antibody responses. Using data from 216 healthy vaccinated donors aged 23-81 years, we evaluated baseline characteristics, prevaccination blood and T-cell phenotypes, and post-vaccination T-cell responses as variables, with anti-receptor-binding domain (RBD) immunoglobulin G (IgG) titers following two doses of BNT162b2 vaccination as the primary outcome. Consistent with previous reports, higher age, a history of allergic disease, and autoimmune disease were associated with lower peak IgG titers. Additionally, the frequencies of interferon-γ+ spike-specific CD4+ T cells (T-cell response) following the first vaccination strongly correlated with higher IgG responses, while those of pre-existing spike-reactive T cells showed no association with peak IgG titers. Furthermore, we identified lower percentages of naïve CD8+ T cells, lower hemoglobin levels, lower lymphocyte counts, and higher mean corpuscular volume as independent pre-vaccination predictors of lower peak IgG levels. Notably, the frequency of naïve CD8+ T cells showed a positive correlation with the peak IgG levels even in univariate analysis. These findings contribute to the individualized prediction of mRNA vaccine efficacy and may provide insights into the mechanisms underlying individual heterogeneity in immune responses.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"403-416"},"PeriodicalIF":4.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663295","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

Zoledronic acid attenuates ischemic brain injury by promoting ETS2 and MSR1 expression. 唑来膦酸通过促进ETS2和MSR1的表达来减轻缺血性脑损伤。

IF 4.8 4区医学

International immunology Pub Date : 2025-06-17 DOI: 10.1093/intimm/dxaf010

Kento Otani, Ryuki Koyama, Jun Tsuyama, Seiichiro Sakai, Koji Hase, Takashi Shichita

{"title":"Zoledronic acid attenuates ischemic brain injury by promoting ETS2 and MSR1 expression.","authors":"Kento Otani, Ryuki Koyama, Jun Tsuyama, Seiichiro Sakai, Koji Hase, Takashi Shichita","doi":"10.1093/intimm/dxaf010","DOIUrl":"10.1093/intimm/dxaf010","url":null,"abstract":"Intracerebral inflammation and brain swelling often worsen the functional prognosis of stroke patients. Post-stroke inflammation is resolved by the removal of inflammatogenic damage-associated molecular patterns (DAMPs) through macrophage scavenger receptor 1 (MSR1); however, therapeutics promoting MSR1 expression efficiently have not been developed. We identified ETS2 as a transcription factor that promoted MSR1 expression in myeloid cells by epigenetic molecular screening. Increased Ets2 expression in macrophages enhanced MSR1 expression and the internalization of peroxiredoxins (PRXs), pivotal inflammatogenic DAMPs in ischemic stroke. By evaluation of chemicals inducing Ets2 expression, we discovered that zoledronic acid increased Ets2 and Msr1 expression in macrophages. Post-stroke administration of zoledronic acid significantly suppressed cerebral inflammation by increasing MSR1 expression in infiltrating myeloid cells, attenuating ischemic neuronal injury in a myeloid Ets2-dependent manner. Thus, epigenetic molecular screening that enhances MSR1 expression is a useful approach to developing therapeutics that improve functional prognosis after ischemic stroke.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"393-402"},"PeriodicalIF":4.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014648","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