International immunology最新文献_第2页

Beyond B cell helpers: diverse roles of peripheral helper T cells. 辅助B细胞之外：外周辅助T细胞的多种作用。

IF 3.4 4区医学

International immunology Pub Date : 2026-09-01 DOI: 10.1093/intimm/dxag025

Yuki Masuo, Hiroyuki Yoshitomi

{"title":"Beyond B cell helpers: diverse roles of peripheral helper T cells.","authors":"Yuki Masuo, Hiroyuki Yoshitomi","doi":"10.1093/intimm/dxag025","DOIUrl":"10.1093/intimm/dxag025","url":null,"abstract":"Peripheral helper T cells (TPH cells) constitute a subset of CD4+ T cells that provide help to B cells in inflamed non-lymphoid tissues. TPH cells have been identified across various chronic disorders, especially autoimmune diseases, and accumulating evidence suggests their involvement in disease pathogenesis. However, the mechanisms by which TPH cells drive persistent inflammation remain incompletely understood. Recent insights reveal that TPH cells play additional roles in local immune responses beyond their classical B cell helper function. In this review, we explore the heterogeneity and functional diversity of TPH cells that contribute to chronic inflammatory processes within target tissues of autoimmunity. These functions of TPH cells include their stem-like capacity to serve as a reservoir and replenish activated cells in situ, as well as their direct role in the activation of macrophages through proinflammatory soluble factors. We further discuss the dynamic interplay between TPH cells and tertiary lymphoid structures (TLSs), highlighting the chemokine regulation for TLS formation and the essential niche these structures offer for the TPH cell maturation. A deeper understanding of TPH cell-mediated tissue inflammation will pave the way for the development of novel therapeutic strategies in persistent autoimmune conditions.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"547-554"},"PeriodicalIF":3.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13529583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147941318","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

Selective decreases in regulatory B-cell (Breg) subsets in active uveitis: IL-10+CD19+CD24hiCD38hiBregs in patients and B10 Bregs in mice. 活动性葡萄膜炎中调节性B细胞（Breg）亚群的选择性降低：患者中的IL-10+CD19+CD24hiCD38hiBreg和小鼠中的B10 Breg。

IF 3.4 4区医学

International immunology Pub Date : 2026-09-01 DOI: 10.1093/intimm/dxag021

Yi-Hsing Chen, Xiaozhe Zhang, Malihe Eskandarpour, Rose M Gilbert, Sue Lightman, Virginia L Calder

{"title":"Selective decreases in regulatory B-cell (Breg) subsets in active uveitis: IL-10+CD19+CD24hiCD38hiBregs in patients and B10 Bregs in mice.","authors":"Yi-Hsing Chen, Xiaozhe Zhang, Malihe Eskandarpour, Rose M Gilbert, Sue Lightman, Virginia L Calder","doi":"10.1093/intimm/dxag021","DOIUrl":"10.1093/intimm/dxag021","url":null,"abstract":"Several regulatory B-cell (Breg) subsets have been implicated in autoimmune diseases. We investigated Breg subsets in non-infectious uveitis (NIU) and in mouse models of experimental autoimmune uveitis (EAU). Blood samples from NIU patients with active disease (n = 13), in remission (n = 37) and healthy controls (n = 10) were immunophenotyped for CD19+CD24hiCD38lo memory B cells, CD19+CD24hiCD38hi-immature Bregs (iBregs), and CD19+CD38intCD24int-mature Bregs. In NIU, levels of peripheral blood iBregs and serum interleukin-10 (IL-10) were decreased in active disease vs. remission (P < .01). In quiescent NIU, iBregs were isolated and, when added at increasing ratios to autologous CD3+ T cells, downregulated T-cell proliferation. In an EAU model, at peak disease, CD19+CD1dhiCD5+ B10, CD19+CD5+ B1, CD19+CD21hiCD24hiCD23+ transitional two marginal-zone precursor (T2-MZP) and CD19+CD21hiCD23- marginal-zone B (MZB) Breg subsets were analysed both phenotypically and functionally. In EAU spleens, all Breg subsets investigated were detectable, but the IL-10-expressing B10-Breg subset was immunosuppressive and inversely correlated with disease severity (P = .048, R2 = 0.47). Blood-derived IL-10-expressing B10 and B1 Bregs were increased in both adjuvant controls and EAU but were significantly reduced in clinically milder EAU. In dissociated retinal cells, only the B10-Breg subset was detectable and increased in EAU. Selective Breg subsets may be immunosuppressive, with iBregs in NIU and IL-10-expressing B10 Bregs in EAU.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"569-580"},"PeriodicalIF":3.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13529577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837609","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

The intestine as a nexus of tissue-encoded immunological memory. 肠道作为组织编码免疫记忆的纽带。

IF 3.4 4区医学

International immunology Pub Date : 2026-09-01 DOI: 10.1093/intimm/dxag024

Mari Murakami, Kiyoshi Takeda

{"title":"The intestine as a nexus of tissue-encoded immunological memory.","authors":"Mari Murakami, Kiyoshi Takeda","doi":"10.1093/intimm/dxag024","DOIUrl":"10.1093/intimm/dxag024","url":null,"abstract":"The intestine is continuously exposed to diverse microbial, dietary, and environmental signals, requiring tightly regulated immune responses that balance host defense and tolerance. Recent advances in single-cell and multiomic technologies have revealed that immune regulation in barrier tissues cannot be fully explained by circulating immune cells but also by coordinated interactions within local tissue microenvironments. In this review, we introduce a conceptual framework that positions the intestine as a hub of tissue-encoded immune programming. Immune states are established through multilayered systems comprising cellular memory, niche memory, and multicellular circuit stabilization across immune, epithelial, and stromal compartments. These programs are reinforced by epigenetic remodeling, transcription factor networks, and metabolic-epigenetic coupling, enabling long-term adaptation to environmental cues. Within the intestinal microenvironment, specialized antigen-sampling pathways and epithelial barrier programs, together with microbiota-derived cues, actively instruct the localization, differentiation, and functional tuning of tissue-adapted immune populations, including tissue-resident memory T cells (TRM). Importantly, these locally imprinted programs can disseminate systemically and influence immune responses in distal tissues. In inflammatory bowel disease, these tissue-encoded immune programs become pathologically stabilized, enabling TRM and multicellular circuits to sustain chronic inflammation even in the absence of ongoing triggering signals. This perspective highlights tissue-encoded immune states as central regulators of immunity and disease.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"537-546"},"PeriodicalIF":3.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147929150","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

PDLIM4 promotes dephosphorylation of STAT transcription factors by recruiting PTP-BL and inhibits Th1, Th2, and Th17 cell differentiation. PDLIM4通过募集PTP-BL促进STAT转录因子去磷酸化，抑制Th1、Th2和Th17细胞分化。

IF 3.4 4区医学

International immunology Pub Date : 2026-09-01 DOI: 10.1093/intimm/dxag019

Aya Jodo, Masakiyo Nakahira, Yuta Kochi, Akiko Sugimoto-Ishige, Tsuneyasu Kaisho, Takashi Tanaka

{"title":"PDLIM4 promotes dephosphorylation of STAT transcription factors by recruiting PTP-BL and inhibits Th1, Th2, and Th17 cell differentiation.","authors":"Aya Jodo, Masakiyo Nakahira, Yuta Kochi, Akiko Sugimoto-Ishige, Tsuneyasu Kaisho, Takashi Tanaka","doi":"10.1093/intimm/dxag019","DOIUrl":"10.1093/intimm/dxag019","url":null,"abstract":"STAT (signal transducers and activators of transcription) transcription factors are activated by tyrosine phosphorylation after cytokine stimulation and are critical for the differentiation of T-helper (Th) cells into particular Th lineage subsets. How STAT-mediated Th cell differentiation is negatively regulated, however, is not fully understood. Here, we report that PDLIM4 binds to STAT3, 4, and 6 and suppresses gene activation mediated by these STATs. PDLIM4 acts as an adaptor that recruits PTP-BL, a protein tyrosine phosphatase, through its LIM (abnormal cell lineage 11-islet 1-mechanosensory abnormal 3) domain, facilitating dephosphorylation of STAT proteins. PDLIM4-deficiency in CD4+ T cells resulted in augmented tyrosine phosphorylation of these STAT proteins and consequently enhanced Th1, Th2, and Th17 cell differentiation, suggesting that PDLIM4 regulates the differentiation of multiple lineages of Th cells by suppressing STAT signaling. We further found that a non-synonymous single-nucleotide polymorphism in PDLIM4, which causes the substitution of a glycine residue with a cysteine in the LIM domain, is associated with susceptibility to rheumatoid arthritis and Graves' disease, both of which are known to be Th17 cell-driven autoimmune diseases. Notably, PDLIM4 containing this amino acid substitution in the LIM domain showed reduced binding to PTP-BL and was therefore partially impaired in its ability to dephosphorylate STAT3 and suppress STAT3 signaling. Our findings define an essential role of PDLIM4 in negatively regulating STAT-mediated Th-cell differentiation and preventing the onset of human autoimmune diseases.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"555-568"},"PeriodicalIF":3.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13529576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770681","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

BNT162b2 mRNA Vaccination Activates Spike-Reactive Regulatory T Cells in Humans. 接种BNT162b2 mRNA可激活人类尖峰反应性调节性T细胞

IF 3.4 4区医学

International immunology Pub Date : 2026-08-24 DOI: 10.1093/intimm/dxag045

Naila Shinwari, Xinxin Xue, Dongyun Lu, Celine Chua, Yayoi Iwamoto, Yuki Masuo, Sho Sekito, Daisuke Akiyama, Yasuhiro Murakawa, Takao Hashiguchi, Isao Ito, Hiroyuki Yoshitomi, Hideki Ueno

{"title":"BNT162b2 mRNA Vaccination Activates Spike-Reactive Regulatory T Cells in Humans.","authors":"Naila Shinwari, Xinxin Xue, Dongyun Lu, Celine Chua, Yayoi Iwamoto, Yuki Masuo, Sho Sekito, Daisuke Akiyama, Yasuhiro Murakawa, Takao Hashiguchi, Isao Ito, Hiroyuki Yoshitomi, Hideki Ueno","doi":"10.1093/intimm/dxag045","DOIUrl":"https://doi.org/10.1093/intimm/dxag045","url":null,"abstract":"Studies using mouse models of viral infection have shown that viral antigen-reactive regulatory T cells play multiple context-dependent roles, including attenuating the immune response against the pathogen and limiting inflammatory damage. By contrast, evidence for the presence and function of viral antigen-specific Tregs in humans remains very limited. Here, we investigated whether BNT162b2 mRNA COVID-19 vaccination activates spike (S)-reactive Tregs in healthy adults. We performed an integrated analysis combining scRNA-seq, TCR repertoire profiling, and flow cytometry of activation-induced marker (AIM) expressing S-reactive CD4+ T cells isolated from PBMCs cultured with trimeric S protein. We found that CD39+ cells co-expressing CTLA4 and TIGIT within the S-reactive AIM+ CD4+ T cell population were preferentially enriched for Tregs relative to their CD39- counterparts. In subjects vaccinated with BNT162b2 mRNA vaccine, the frequencies of CD39+CTLA4+ and CD39+TIGIT+ S-reactive Treg-like cells were significantly increased following vaccination. Using scRNA-seq, we identified two FoxP3+ Treg clusters among S-reactive CD4+ T cells: one characterized by IFN-activated gene signatures and another by high HLA class II, CD39 and CTLA4 expression. Both subsets were transcriptionally activated following vaccination, with upregulation of genes associated with T cell activation and inflammatory cytokines including TNF and IFNG. Consistent with these findings, flow cytometry detected increased proportions of CD39+ and FoxP3+ S-reactive Tregs expressing IFN-γ and/or TNF-α following vaccination. Collectively, these findings support a model in which BNT162b2 mRNA vaccination activates both an S-reactive effector T cell response and a Treg response, suggesting Treg co-induction may be critical for balancing antiviral immunity with immunoregulation.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808630","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

Redefining long-lived plasma cells by timestamping: isotype- and tissue-specific logic of plasma cell longevity. 通过时间戳重新定义长寿的浆细胞：同型和组织特异性的浆细胞寿命逻辑。

IF 3.4 4区医学

International immunology Pub Date : 2026-08-19 DOI: 10.1093/intimm/dxag046

Wataru Ise

引用次数: 0

Bispecific antibodies: current advances and future perspectives. 双特异性抗体：当前进展和未来展望。

IF 3.4 4区医学

International immunology Pub Date : 2026-08-18 DOI: 10.1093/intimm/dxag044

Toshiya Hino, Yusuke Ito, Yuki Kagoya

{"title":"Bispecific antibodies: current advances and future perspectives.","authors":"Toshiya Hino, Yusuke Ito, Yuki Kagoya","doi":"10.1093/intimm/dxag044","DOIUrl":"https://doi.org/10.1093/intimm/dxag044","url":null,"abstract":"Bispecific antibodies (BsAbs) are emerging immunotherapeutics that simultaneously engage two distinct targets. This property provides unique mechanisms of action that are not achieved by conventional monoclonal antibodies, including cell-cell bridging, modulation of multiple signaling pathways, and recruitment of diverse immune effector cells. Among these approaches, T cell-engaging BsAbs are the most established modality. By simultaneously targeting a tumor-associated antigen and CD3 on T cells, they promote tumor-T cell bridging, immune synapse formation, and MHC-independent T cell activation, and have shown marked clinical efficacy in several hematologic malignancies. More recently, their application has been extended to solid tumors, supported by encouraging data from clinical trials. Despite these advances, the efficacy and safety of BsAbs face several limitations, including short half-lives, tumor antigen escape, off-tumor toxicity, and insufficient T cell activation due to the lack of costimulatory signals. To address these obstacles, BsAb structures have been modified in various ways, including Fc fusion, multispecific targeting, and armored designs that enhance T cell function. These approaches aim to improve pharmacokinetics, specificity, and antitumor efficacy. In addition to these efforts, novel delivery platforms have been developed to further enhance the therapeutic potential of BsAbs. Engineered extracellular vesicles and nanoparticle-based systems may improve pharmacokinetics and tumor delivery, while enabling the integration of additional functional molecules beyond conventional BsAb formats. In this review, we summarize the basic principles of BsAbs, highlight key clinical developments, and discuss emerging strategies and remaining challenges in the development of next-generation BsAbs.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792556","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

Healthy ageing: The struggle for maintaining T cells young. 健康衰老：为保持T细胞年轻而斗争。

IF 3.4 4区医学

International immunology Pub Date : 2026-08-13 DOI: 10.1093/intimm/dxag042

David Frieser, Noemie Gensous, Victor Appay

引用次数: 0

Single-cell landscape of neutrophil activation in primary sclerosing cholangitis. 原发性硬化性胆管炎中性粒细胞活化的单细胞景观。

IF 3.4 4区医学

International immunology Pub Date : 2026-08-11 DOI: 10.1093/intimm/dxag043

Lynn Zreka, Hajime Morita, Shuhe Ma, Toshiaki Bando, Mouna Khan, Yuki Masuo, Shunsuke Uno, Hirotaka Sato, Joey Matsuyama, Shinya Okumura, Takashi Ito, Etsuro Hatano, Suzanne Alshemali, Hiroyuki Yoshitomi, Hideki Ueno

{"title":"Single-cell landscape of neutrophil activation in primary sclerosing cholangitis.","authors":"Lynn Zreka, Hajime Morita, Shuhe Ma, Toshiaki Bando, Mouna Khan, Yuki Masuo, Shunsuke Uno, Hirotaka Sato, Joey Matsuyama, Shinya Okumura, Takashi Ito, Etsuro Hatano, Suzanne Alshemali, Hiroyuki Yoshitomi, Hideki Ueno","doi":"10.1093/intimm/dxag043","DOIUrl":"https://doi.org/10.1093/intimm/dxag043","url":null,"abstract":"Primary sclerosing cholangitis (PSC) is a chronic autoimmune cholestatic liver disease characterized by progressive inflammation and fibrosis, but the role of neutrophils in PSC remains poorly understood. To define neutrophil states in the PSC liver microenvironment, we performed single-cell RNA sequencing of leukocytes isolated from liver perfusate obtained from healthy donor grafts and explanted PSC livers. We identified a marked expansion of transcriptionally diverse neutrophil subclusters in PSC liver perfusate. Importantly, PSC livers were enriched for four neutrophil subclusters: RHOB-high, immediate early gene-high, heat shock protein-high, and CXCL8-high liver neutrophil-like subclusters. These PSC-associated neutrophil subclusters showed increased activity of the TNF and IL-17 signaling pathways, consistent with current views of PSC pathogenesis. They also displayed activation of inflammatory transcriptional regulators, including CEBPB, JUN, FOS, and RELA. Pseudotime analysis suggested that RHOB and immediate early gene subsets were derived from immature neutrophils, whereas liver neutrophil-like and heat shock protein-high subsets exhibited more mature and tissue-adapted features. Together, these data reveal previously unrecognized heterogeneity of liver neutrophils in PSC and identify inflammatory neutrophil programs that may contribute to sustained hepatic inflammation and represent potential therapeutic targets.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706285","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

Lipid metabolic regulation of pathogenic type 2 immunity in the airway. 气道致病性2型免疫的脂质代谢调节。

IF 3.4 4区医学

International immunology Pub Date : 2026-08-01 DOI: 10.1093/intimm/dxag015

Hiroyuki Yagyu, Masahiro Kiuchi, Kiyoshi Hirahara

{"title":"Lipid metabolic regulation of pathogenic type 2 immunity in the airway.","authors":"Hiroyuki Yagyu, Masahiro Kiuchi, Kiyoshi Hirahara","doi":"10.1093/intimm/dxag015","DOIUrl":"10.1093/intimm/dxag015","url":null,"abstract":"Immune memory is central to host protection against pathogens and contributes to the pathogenesis of chronic inflammatory diseases. Beyond canonical cytokines and antigenic stimuli, metabolic signals have emerged as pivotal regulators of T-cell activation, differentiation, and memory formation. However, the mechanisms by which metabolic and tissue-derived cues imprint pathogenic features on T cells remain poorly understood. Dysregulation of type 2 immune memory is a major driver of chronic inflammation in allergic diseases. A distinct subpopulation of memory T helper 2 (Th2) cells that express the interleukin (IL)-33 receptor ST2 has emerged as a key contributor to the pathogenesis of chronic allergic inflammation. Recent studies have revealed a close link between lipid metabolism and pathogenic type 2 immunity, highlighting how fatty acid uptake, storage within lipid droplets, and catabolism through lipolysis and lipophagy regulate the expression of ST2 and cytokine production. Moreover, transcriptional regulators such as peroxisome proliferator-activated receptor γ (PPARγ) integrate lipid-derived signals with transcriptional and metabolic programs that induce pathogenic memory. In this review, we summarize the current understanding of CD4+ T cell-mediated immune memory, with a particular focus on pathogenic Th2 cells and airway type 2 immunity, and discuss emerging concepts that connect lipid metabolic programs, transcriptional regulation, and chronic allergic inflammation.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"469-481"},"PeriodicalIF":3.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698561","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