International immunology最新文献

IL-5-producing Group 2 innate lymphoid cells promote T cell-independent IgA production in cooperation with eosinophils. 产生 IL-5 的第 2 组先天性淋巴细胞与嗜酸性粒细胞合作，促进不依赖 T 细胞的 IgA 生成。

IF 4.8 4区医学

International immunology Pub Date : 2025-04-07 DOI: 10.1093/intimm/dxae070

Tsutomu Yanagibashi, Masashi Ikutani, Terumi Nagai, Makoto Arita, Yasuharu Watanabe, Yoshinori Nagai, Kiyoshi Takatsu

{"title":"IL-5-producing Group 2 innate lymphoid cells promote T cell-independent IgA production in cooperation with eosinophils.","authors":"Tsutomu Yanagibashi, Masashi Ikutani, Terumi Nagai, Makoto Arita, Yasuharu Watanabe, Yoshinori Nagai, Kiyoshi Takatsu","doi":"10.1093/intimm/dxae070","DOIUrl":"10.1093/intimm/dxae070","url":null,"abstract":"Intestinal bacteria play a critical role in the regulation of the host immune system and an imbalance in the intestinal bacterial composition induces various host diseases. Therefore, maintaining a balance in the intestinal bacterial composition is crucial for health. Immunoglobulin A (IgA), produced through T cell-dependent and T cell-independent (TI) pathways, is essential for host defense against pathogen invasion and maintaining the balance of intestinal symbiotic bacteria. Interleukin (IL)-5 is constitutively produced by Group 2 innate lymphoid cells (ILC2s) and plays a critical role in the survival and proliferation of B cells and eosinophils. Here, we show the role of IL-5-producing ILC2s in intestinal TI IgA production at steady state using T cell receptor α deficient mice. In this mouse model, ILC2s increased fecal TI IgA levels in a non-inflammatory state in an IL-5-dependent manner. The administration of recombinant IL-33 (rIL-33) increased the amount of TI IgA production, accompanied by an increase in the number of IL-5-producing ILC2s in the large intestine. In addition, rIL-33 treatment increased IL-5-dependent IgA+ cells in isolated lymphoid follicles, the site of TI IgA production. Furthermore, eosinophils recruited by ILC2s were required for the maximal production of IgA in the TI pathway. Moreover, IL-5 increased the frequency of TI IgA-binding intestinal bacteria and was involved in the maintenance of intestinal bacterial composition. These findings indicate that IL-5-producing ILC2s together with eosinophils contribute to TI IgA production. In addition to their role in TI IgA production, IL-5-producing ILC2s may contribute to the homeostasis of intestinal commensal bacteria.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"273-285"},"PeriodicalIF":4.8,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828467","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

A complex of NLRP3 with caspase-4 is essential for inflammasome activation by Tannerella forsythia infection. NLRP3与caspase-4的复合物对于连翘Tannerella感染的炎性体激活至关重要。

IF 4.8 4区医学

International immunology Pub Date : 2025-04-07 DOI: 10.1093/intimm/dxae071

Chen-Wei Hsu, Tokuju Okano, Yuiko Niinuma, Anongwee Leewananthawet, Tamako Iida, Poramed Onsoi, Kotchakorn Boonyaleka, Hiroshi Ashida, Toshihiko Suzuki

{"title":"A complex of NLRP3 with caspase-4 is essential for inflammasome activation by Tannerella forsythia infection.","authors":"Chen-Wei Hsu, Tokuju Okano, Yuiko Niinuma, Anongwee Leewananthawet, Tamako Iida, Poramed Onsoi, Kotchakorn Boonyaleka, Hiroshi Ashida, Toshihiko Suzuki","doi":"10.1093/intimm/dxae071","DOIUrl":"10.1093/intimm/dxae071","url":null,"abstract":"Periodontitis, a chronic inflammatory disease of periodontal tissue, is often associated with a group of pathogenic bacteria known as the \"red complex\", including Tannerella forsythia. Previous papers showed that T. forsythia induces many kinds of inflammatory cytokines including interleukin (IL)-1β regulated by inflammasome activation. However, the physiological function of periodontitis and the mechanism to induce inflammasome activation by T. forsythia infection are poorly understood. In this study, we demonstrate that the Nod-like receptor pyrin domain containing 3 (NLRP3) and caspase-4 are essential for inflammasome activation by T. forsythia infection, playing a crucial role in IL-1β maturation in THP-1 cells. We also showed that the knockout of ASC or Gasdermin D suppresses pyroptotic cell death. Moreover, co-immunoprecipitation assays confirmed the formation of a complex involving caspase-4, NLRP3, and ASC following T. forsythia infection. Additionally, reactive oxygen species production was identified as a key factor in caspase-4-mediated NLRP3 inflammasome activation by T. forsythia infection. These results enhance our understanding of inflammasome activation in response to T. forsythia infection and provide new insights into the pathogenic mechanisms of periodontitis.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"261-271"},"PeriodicalIF":4.8,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824347","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

Cancer immunotherapy in progress-an overview of the past 130 years. 癌症免疫治疗进展——过去130年的综述。

IF 4.8 4区医学

International immunology Pub Date : 2025-04-07 DOI: 10.1093/intimm/dxaf002

Hiroaki Ikeda

引用次数: 0

Analysis of antigen specificity of Treg clonotypes expanded upon SARS-CoV-2 infection. SARS-CoV-2感染扩增的Treg细胞克隆型抗原特异性分析。

IF 4.8 4区医学

International immunology Pub Date : 2025-04-07 DOI: 10.1093/intimm/dxae072

Yukiko Takeuchi, Eri Ishikawa, Takashi Sato, Masaharu Shinkai, Yoshimasa Takahashi, Xiuyuan Lu, Sho Yamasaki

{"title":"Analysis of antigen specificity of Treg clonotypes expanded upon SARS-CoV-2 infection.","authors":"Yukiko Takeuchi, Eri Ishikawa, Takashi Sato, Masaharu Shinkai, Yoshimasa Takahashi, Xiuyuan Lu, Sho Yamasaki","doi":"10.1093/intimm/dxae072","DOIUrl":"10.1093/intimm/dxae072","url":null,"abstract":"The pandemic outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has threatened human health worldwide. Among protective immune reactions, T cell responses are diverse among individuals, which is related to the differences in severity. A T cell subset, regulatory T (Treg) cells, is crucial for limiting excessive immune responses. If SARS-CoV-2-specific Tregs are developed during infection, they may counteract antiviral immunity and cause severe symptoms. To address this possibility, we conducted single-cell TCR-RNA-sequencing of peripheral blood mononuclear cells from convalescent Coronavirus disease 2019 (COVID-19) patients. Among 13 donors, one with severe symptoms had substantially more FOXP3-expressing Treg clonotypes activated in the presence of SARS-CoV-2 virion or other major antigen proteins. To define the reactivity of these Treg clonotypes, 15 highly expanded Treg clonotypes were reconstituted into reporter cells and stimulated with 27 distinct peptide pools that cover all SARS-CoV-2 proteins. However, none of these clonotypes react to any SARS-CoV-2 antigens. Instead, the reporter cells expressing one TCR clonotype (23599) were activated in the presence of Epstein-Barr virus-transformed B cells without adding exogenous antigens. Furthermore, 23599 TCR-expressing cells were activated by non-transformed naïve syngeneic B cells in a DQA1*03:03-DQB1*04:01-dependent manner, suggesting that clonotype 23599 may be autoreactive. This Treg clonotype, 23599, was also detected in a public TCR database and significantly expanded in COVID-19 patients compared to healthy donors. These results suggest that SARS-CoV-2 is not the dominant antigen inducing Treg cells during infection.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"287-293"},"PeriodicalIF":4.8,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812384","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 : 2025-03-29 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":"https://doi.org/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 of 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 (CNS). NA activates the IL-6 amplifier, which leads to the hyper-activation of 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, 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":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-29","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

Immunogenomic precision medicine: a personalized approach based on immunogenomic cancer evolution. 免疫基因组精准医学：基于免疫基因组癌症进化的个性化方法。

IF 4.8 4区医学

International immunology Pub Date : 2025-03-29 DOI: 10.1093/intimm/dxaf020

Yusaku Momoi, Shogo Kumagai, Hiroyoshi Nishikawa

{"title":"Immunogenomic precision medicine: a personalized approach based on immunogenomic cancer evolution.","authors":"Yusaku Momoi, Shogo Kumagai, Hiroyoshi Nishikawa","doi":"10.1093/intimm/dxaf020","DOIUrl":"https://doi.org/10.1093/intimm/dxaf020","url":null,"abstract":"Cancer progression can be understood as a process of diversification and selection (the evolutionary theory of cancer). The immune system also plays a critical role in this process of diversification and selection. The cancer immunoediting hypothesis provides a partial explanation of this evolutionary process; immune-evading cancer clones with genomic and/or epigenomic alterations are selected under the pressure of immune surveillance and can become equipped with multiple immunosuppressive mechanisms, leading to the development of clinically apparent cancers. Indeed, inflammatory cancers equip immunosuppressive mechanisms in response to the pressure of the immune system. However, recent studies focusing on human cancers have revealed that certain non-inflammatory cancers, which often harbor a single driver oncogenic mutation, are equipped with immunosuppressive machinery sufficient to evade immune surveillance at the time of malignant transformation. The sequential model of the cancer immunoediting hypothesis is inadequate to explain the development of these non-inflammatory cancers, highlighting the need for a novel concept that can explain their co-evolutionary processes. Moreover, inhibition of oncogenic signaling by specific driver oncogenes has been shown not only to kill cancer cells but also to augment antitumor immunity, suggesting the potential for the advent of molecularly targeted reagents with a variety of immunomodulatory functions from the perspective of personalized therapies. Here, we discuss the processes by which cancer cells and the immune system co-evolve to establish clinically apparent cancers, thereby introducing a new concept of 'immunogenomic cancer evolution', that provides a rationale for the potential of personalized 'immunogenomic cancer precision medicine'.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742802","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

TAK1 Governs Monocyte-Derived Macrophage Development in Acute Sterile Peritonitis. TAK1控制急性无菌腹膜炎中单核细胞来源的巨噬细胞的发育。

IF 4.8 4区医学

International immunology Pub Date : 2025-03-29 DOI: 10.1093/intimm/dxaf019

Katsuki Iwahori, Kengo Maeda, Hideki Sanjo

{"title":"TAK1 Governs Monocyte-Derived Macrophage Development in Acute Sterile Peritonitis.","authors":"Katsuki Iwahori, Kengo Maeda, Hideki Sanjo","doi":"10.1093/intimm/dxaf019","DOIUrl":"https://doi.org/10.1093/intimm/dxaf019","url":null,"abstract":"Monocytes recruited to inflamed tissues differentiate into macrophages, contributing to the resolution of inflammation and tissue repair. However, the mechanisms underlying the development, differentiation, and maturation of these monocyte-derived macrophages (MOMs) remain incompletely understood. Here, we demonstrate that TGFβ-activated kinase 1 (TAK1), a key signaling mediator downstream of various receptors including cytokine receptors and Toll-like receptors, is essential for MOM development. In a zymosan-induced model of acute sterile peritonitis, mice with myeloid-specific deletion of TAK1 exhibited a severe impairment in MOM development within the peritoneal cavity, in contrast to control mice. Blocking death receptor signaling with neutralizing antibodies facilitated the recovery of MOM development in these mice, albeit to a limited extent. We identified a transient population of immediate macrophage precursors differentiating from infiltrating monocytes in the peritoneal cavity. Notably, TAK1-deficient macrophage precursors displayed marked susceptibility to cell death, possibly due to a previously unrecognized mechanism distinct from well-characterized cell death pathways. These findings establish TAK1 as a critical regulator of MOM development and uncover a novel survival mechanism in the macrophage precursors during inflammation.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742804","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

Immune responses underpinning acute co-infections with unrelated viruses: timing and location matter. 支持与不相关病毒急性合并感染的免疫反应：时间和地点问题。

IF 4.8 4区医学

International immunology Pub Date : 2025-03-24 DOI: 10.1093/intimm/dxaf018

Isabelle Jia Hui Foo, Lukasz Kedzierski, Katherine Kedzierska

{"title":"Immune responses underpinning acute co-infections with unrelated viruses: timing and location matter.","authors":"Isabelle Jia Hui Foo, Lukasz Kedzierski, Katherine Kedzierska","doi":"10.1093/intimm/dxaf018","DOIUrl":"https://doi.org/10.1093/intimm/dxaf018","url":null,"abstract":"Immunity to viral infections is generally studied in isolation by measuring immune responses towards a single virus. However, concurrent or sequential viral co-infections can occur in a single host. Viral co-infections can impact antiviral immunity by altering protective responses and driving immunopathology. Understanding immune mechanisms towards co-infections with unrelated viruses is highly relevant to treatment and prevention. There is, however, paucity of data on immune responses towards viral co-infections, especially with unrelated viruses. Most commonly studied viral co-infections include chronic viruses, such as hepatitis B, hepatitis C and human immunodeficiency virus (HIV), as well as viruses infecting the same tissues, including respiratory viral co-infections. However, the immunological consequences of co-infections with unrelated acute viruses are less understood, especially for viruses affecting different anatomical sites. As co-infecting viruses can have a more pronounced impact on human health compared to infection with a single virus, understanding immune responses and, especially, the impact of timing, sequence and location of viral co-infections is of key importance. This review provides an overview of the current knowledge on acute viral co-infections with unrelated viruses, underpinning immune mechanisms and implications for vaccination regimens.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700019","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

Tertiary lymphoid structures: chronic inflammatory microenvironments in kidney diseases. 三级淋巴样结构：肾脏疾病的慢性炎症微环境。

IF 4.8 4区医学

International immunology Pub Date : 2025-03-24 DOI: 10.1093/intimm/dxaf017

Takahisa Yoshikawa, Motoko Yanagita

{"title":"Tertiary lymphoid structures: chronic inflammatory microenvironments in kidney diseases.","authors":"Takahisa Yoshikawa, Motoko Yanagita","doi":"10.1093/intimm/dxaf017","DOIUrl":"https://doi.org/10.1093/intimm/dxaf017","url":null,"abstract":"Chronic kidney disease is a global health problem with high morbidity and mortality rates. Acute kidney injury substantially increases the risk of chronic kidney disease progression, particularly in the elderly, partly because of prolonged inflammation that exacerbates kidney fibrosis and dysfunction. Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates that develop in non-lymphoid organs during chronic inflammation, such as autoimmune diseases, cancers, and age-related inflammation. Age-dependent TLS formation is observed in various organs, such as the kidneys, bladders, lacrimal glands, and liver, potentially contributing to age-related disorders, including chronic kidney disease progression after acute kidney injury. TLSs contain heterogeneous cell populations, such as T cells, B cells, pro-inflammatory fibroblasts, and blood and lymphatic vessels, which orchestrate TLS development and expansion through intensive cell-cell interactions. Pro-inflammatory fibroblasts within TLSs drive TLS formation by producing various chemokines and cytokines that recruit and activate immune cells. Additionally, the CD153-CD30 signaling pathway between senescence-associated T cells and age-associated B cells, both of which increase with age, are essential for renal TLS maturation and expansion, which could be a promising therapeutic target in kidney injury in aged individuals. TLSs also develop in human kidney diseases, such as various glomerulopathies, transplanted kidneys, and renal cell carcinomas, thereby influencing patient outcomes. This review highlights the recent advances in our understanding of the cellular and molecular mechanisms underlying TLS development and pathogenicity, with a focus on age-dependent TLSs in the kidneys. Furthermore, the clinical relevance of TLSs in human kidney diseases is discussed.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700222","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

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 : 2025-03-21 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":"https://doi.org/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":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-21","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