International immunology最新文献_第7页

Vaccine adjuvants as stand-alone immunoprophylaxis in strategies for 100-day rapid responses to future pandemics. 疫苗佐剂作为未来流行病100天快速反应战略中的独立免疫预防

IF 3.4 4区医学

International immunology Pub Date : 2026-02-09 DOI: 10.1093/intimm/dxaf053

Niloufar Kavian, Kouji Kobiyama, Ken J Ishii, Cevayir Coban

引用次数: 0

Molecular mechanisms for direct sensing of virus-like antigens by B cells. B细胞直接感知病毒样抗原的分子机制。

IF 3.4 4区医学

International immunology Pub Date : 2026-02-09 DOI: 10.1093/intimm/dxaf052

Wei Cheng, Julie Zikherman

{"title":"Molecular mechanisms for direct sensing of virus-like antigens by B cells.","authors":"Wei Cheng, Julie Zikherman","doi":"10.1093/intimm/dxaf052","DOIUrl":"10.1093/intimm/dxaf052","url":null,"abstract":"Particulate antigens (Ags) such as viruses can often induce strong B-cell responses in vivo very effectively, but the molecular determinants of this complex process remain incompletely understood. In this review, we focus on recent mechanistic insights into the earliest steps in the initiation of primary B-cell responses to viruses, gained by exploiting a new generation of model particulate Ag, synthetic virus-like structures. We also review the characteristics of the resulting short- and long-term antibody (Ab) responses in mice. These studies reveal that a repeating pattern of epitope display on a virus-sized scaffold is a fundamental biophysical feature of viruses that triggers a qualitatively distinct mode of B-cell Ag receptor (BCR) signal transduction relative to soluble Ag display, and consequently serves as a standalone danger signal for Ag-specific B-cell activation. Quantitative variation in epitope density (ED) on such scaffolds modulates the degree and quality of B-cell activation both in vitro and in vivo. The presence of internal nucleic acid (iNA) in the interior of these virus-like structures can profoundly influence the resulting Ab responses for the lifespan of immunized animals. We conclude that the ED of viral surface Ags and the iNA genomes provide two essential signals that together are sufficient for B-cell activation and Ab production during antiviral responses. We place these findings in the context of the literature, discuss implications for rational vaccine design, and highlight unanswered questions to guide future research directions.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"74-84"},"PeriodicalIF":3.4,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13327809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952955","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

Role of Themis in peripheral CD8 T cells in hapten-induced allergic skin inflammation. 外周CD8 T细胞Themis在半抗原诱导的过敏性皮肤炎症中的作用。

IF 3.4 4区医学

International immunology Pub Date : 2026-02-09 DOI: 10.1093/intimm/dxaf050

Masayuki Kitajima, Toshiyuki Okada, Kenta Nakano, Tadashi Okamura, Harumi Suzuki

{"title":"Role of Themis in peripheral CD8 T cells in hapten-induced allergic skin inflammation.","authors":"Masayuki Kitajima, Toshiyuki Okada, Kenta Nakano, Tadashi Okamura, Harumi Suzuki","doi":"10.1093/intimm/dxaf050","DOIUrl":"10.1093/intimm/dxaf050","url":null,"abstract":"Themis (thymocyte-expressed molecule involved in selection) is a T-cell-specific protein that is critically required for positive selection in the thymus. However, its function in T-cell receptor (TCR) responses during allergic skin inflammation remains unclear. To investigate the function of Themis in peripheral T cells, we generated tamoxifen-induced Themis conditional knockout (cKO) mice. The deletion of Themis by tamoxifen treatment significantly reduced ear swelling and CD8 T-cell infiltration induced by hapten 2,4-dinitrofluorobenzene (DNFB) challenge, which activates CD8 T cells. The CD8 T cells in the inflamed skin from Themis cKO mice showed decreased interferon gamma (IFNγ) production and T-bet and Eomes expression. Furthermore, the transgenic overexpression of Themis enhanced DNFB-induced allergic skin responses. However, Themis cKO mice showed unaltered skin inflammation induced by fluorescein isothiocyanate/dibutyl phthalate, which activates CD4 T cells. The TCR-stimulated proliferation and IFNγ production of Themis cKO naïve CD8 T cells were significantly decreased in vitro, whereas the proliferation and cytokine production of CD4 T cells were not altered. As expected, the administration of the SHP-1/2 inhibitor restored the reduced IFNγ production in Themis cKO CD8 T cells in vitro. Mice harboring mutant Themis lacking the Grb2-binding site showed a similar phenotype to Themis cKO mice, indicating that the function of Themis in peripheral CD8 T cells is dependent on Grb2 binding. Collectively, these results suggest that Themis regulates the threshold of TCR signaling in peripheral CD8 T cells, but not in CD4 T cells.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"107-117"},"PeriodicalIF":3.4,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952884","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

Correction to: Single-cell multiomic analysis revealed the differentiation, localization, and heterogeneity of IL10+ Foxp3- follicular T cells in humans. 更正：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 3.4 4区医学

International immunology Pub Date : 2026-01-14 DOI: 10.1093/intimm/dxaf059

引用次数: 0

TCR representation learning with protein language models: a comprehensive review. 蛋白质语言模型的TCR表示学习综述。

IF 3.4 4区医学

International immunology Pub Date : 2026-01-14 DOI: 10.1093/intimm/dxaf048

Kyohei Kinoshita, Tetsuya J Kobayashi

{"title":"TCR representation learning with protein language models: a comprehensive review.","authors":"Kyohei Kinoshita, Tetsuya J Kobayashi","doi":"10.1093/intimm/dxaf048","DOIUrl":"10.1093/intimm/dxaf048","url":null,"abstract":"The T-cell receptor (TCR) repertoire is a valuable source of information that reflects an individual's immune status and infection history. However, due to the exceptional diversity and complexity of the TCR repertoire, predicting its functional properties remains a challenging task. This review summarizes recent advances in protein language models (PLMs), which apply natural language processing techniques to protein sequences, focusing specifically on TCR repertoire analysis. We begin by outlining the biological basis of the TCR repertoire and its current clinical applications. We then describe the methods used for representing TCR data and the training procedures of the corresponding PLMs. PLMs capture context-dependent features from large unlabeled TCR datasets and achieve high generalization performance even with limited labeled data through transfer learning. In this respect, PLMs offer significant advantages over conventional sequence representation methods. We highlight antigen specificity prediction as a key application, comparing supervised deep learning models with PLM-based approaches. While employment of PLMs is promising, TCR repertoire analysis still faces challenges such as data scarcity, bias, and lack of paired-chain information. Addressing these challenges requires rigorous dataset optimization, integration, and augmentation strategies. Future advances will require better interpretation of the representations learned by PLMs and the development of multimodal approaches that integrate structural information. These advances could enable several clinical applications, including disease diagnosis, vaccine development, and personalized immune profiling.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"15-27"},"PeriodicalIF":3.4,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12802949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952902","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

Anti-human TLR7 antibody for therapeutic intervention in systemic lupus erythematosus. 抗人TLR7抗体对系统性红斑狼疮的治疗干预作用。

IF 3.4 4区医学

International immunology Pub Date : 2026-01-14 DOI: 10.1093/intimm/dxaf046

Ryutaro Fukui, Yusuke Murakami, Atsuo Kanno, Yuji Motoi, Atsushi Manno, Tomohiro Honda, Shinnosuke Yamada, Jun Ishiguro, Takashi Kagari, Kensuke Nakamura, Michinori Kadokura, Takashi Isobe, Yoshiaki Tomimori, Jun Tanaka, Giorgio Senaldi, Toshiyuki Shimizu, Kensuke Miyake

{"title":"Anti-human TLR7 antibody for therapeutic intervention in systemic lupus erythematosus.","authors":"Ryutaro Fukui, Yusuke Murakami, Atsuo Kanno, Yuji Motoi, Atsushi Manno, Tomohiro Honda, Shinnosuke Yamada, Jun Ishiguro, Takashi Kagari, Kensuke Nakamura, Michinori Kadokura, Takashi Isobe, Yoshiaki Tomimori, Jun Tanaka, Giorgio Senaldi, Toshiyuki Shimizu, Kensuke Miyake","doi":"10.1093/intimm/dxaf046","DOIUrl":"10.1093/intimm/dxaf046","url":null,"abstract":"Toll-like receptor 7 (TLR7) is an endosomal sensor that responds to both pathogen-derived and self-derived single-stranded RNA (ssRNA). Responses of TLR7 to self-derived ssRNA have been implicated in the development of autoimmune diseases, such as systemic lupus erythematosus (SLE). TLR7 antagonists and inhibitory anti-TLR7 monoclonal antibodies (mAbs) can protect lupus-prone NZBWF1 mice from lethal nephritis. However, less is known about TLR7 dependence and activation in human SLE, as both TLR7 and TLR8 respond to ssRNA in humans. Here, we analyzed public databases and found that TLR7 gene signature scores were consistently elevated across datasets, races, and SLEDAI scores compared to TLR8, suggesting a deeper involvement of TLR7 in SLE pathogenesis. To specifically inhibit human TLR7 responses, we developed inhibitory mAbs against human TLR7. Utilizing an inhibitory clone, we generated the humanized mAb, DS-7011a. DS-7011a effectively inhibited TLR7-mediated responses in plasmacytoid dendritic cells (pDCs) and B cells. Furthermore, DS-7011a was internalized in a TLR7-dependent manner and accumulated in B cells, pDCs, conventional dendritic cells (cDCs), and monocytes/macrophages. In this study, we describe the generation and preclinical development of DS-7011a, which has the potential to be a therapeutic option for the treatment of SLE.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"28-40"},"PeriodicalIF":3.4,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12802918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000402","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

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 3.4 4区医学

International immunology Pub Date : 2026-01-14 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":"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":"5-14"},"PeriodicalIF":3.4,"publicationDate":"2026-01-14","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

Oligoclonal expansion of IgG+ B cells along with Tfh cell response is associated with a better outcome in endometrial cancer. IgG+ B细胞的寡克隆扩增与Tfh细胞反应与子宫内膜癌更好的预后相关。

IF 3.4 4区医学

International immunology Pub Date : 2026-01-14 DOI: 10.1093/intimm/dxaf049

Mayu Fujioka, Shusei Fujioka, Hiroyuki Yoshitomi, Junzo Hamanishi, Haruka Suzuki, Masayo Ukita, Yasuhide Takeuchi, Sachiko Minamiguchi, Hiroaki Ito, Masaki Mandai, Hideki Ueno

{"title":"Oligoclonal expansion of IgG+ B cells along with Tfh cell response is associated with a better outcome in endometrial cancer.","authors":"Mayu Fujioka, Shusei Fujioka, Hiroyuki Yoshitomi, Junzo Hamanishi, Haruka Suzuki, Masayo Ukita, Yasuhide Takeuchi, Sachiko Minamiguchi, Hiroaki Ito, Masaki Mandai, Hideki Ueno","doi":"10.1093/intimm/dxaf049","DOIUrl":"10.1093/intimm/dxaf049","url":null,"abstract":"B cells play a critical role in tumor immunity, with their presence associated with improved prognosis in various cancers, including endometrial cancer (EC). However, the nature of the B-cell response within the tumor microenvironment (TME) remains incompletely understood. In this study, we conducted single-cell analyses of B cells and CD4+ T cells in the TME of EC. We found that the TME of EC harbored abundant plasmablasts and plasma cells (PCs), which were rare in normal endometria. PCs primarily expressed either IgG or IgA, and a high abundance of IgG in TME was associated with better overall survival. B-cell receptor (BCR) repertoire analysis revealed a clonal expansion of IgG+ B cells, coinciding with an increased presence of T follicular helper (Tfh) cells in the TME. Notably, Tfh cells shared T-cell receptor clones with cycling CD4+ T cells, indicating local proliferation. BCR repertoire analysis also suggested that IgG+ PCs differentiate from IFN-responding B cells and double-negative B cells in the TME. Additionally, recombinant oligoclonal IgG antibodies were found to recognize antigens expressed by tumor cells as well as normal endometrial cells. Collectively, our study shows that the clonal expansion of IgG+ B cells, along with the Tfh cell response, is associated with a better outcome in EC.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"56-67"},"PeriodicalIF":3.4,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015166","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 role of IL-4+ memory T cells in SARS-CoV-2 booster vaccination. IL-4+记忆T细胞在SARS-CoV-2加强疫苗接种中的作用

IF 3.4 4区医学

International immunology Pub Date : 2026-01-14 DOI: 10.1093/intimm/dxaf051

Jumana Khalil, Kosuke Miyauchi, Yoshie Suzuki, Sewon Ki, Yasuyo Harada, Takanori Sasaki, Yuichiro Yamamoto, Rina Hashimoto, Takako Yamamoto, Masashi Matsuda, Haruhiko Koseki, Manabu Nakayama, Masayoshi Fukasawa, Takaji Wakita, Hideki Ueno, Kohji Noguchi, Kazuo Takayama, Masato Kubo

{"title":"The role of IL-4+ memory T cells in SARS-CoV-2 booster vaccination.","authors":"Jumana Khalil, Kosuke Miyauchi, Yoshie Suzuki, Sewon Ki, Yasuyo Harada, Takanori Sasaki, Yuichiro Yamamoto, Rina Hashimoto, Takako Yamamoto, Masashi Matsuda, Haruhiko Koseki, Manabu Nakayama, Masayoshi Fukasawa, Takaji Wakita, Hideki Ueno, Kohji Noguchi, Kazuo Takayama, Masato Kubo","doi":"10.1093/intimm/dxaf051","DOIUrl":"10.1093/intimm/dxaf051","url":null,"abstract":"Vaccines effectively stimulate protective immune responses in healthy individuals, but the precise roles of germinal center (GC) and follicular helper T (TFH) cells in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine responses are not fully understood. This study used a conditional loss-of-function mouse model to investigate antibody responses to the Wuhan spike protein, specifically eliminating newly developed TFH cells during either the primary or memory phase. Our findings demonstrated that TFH-mediated GC responses are essential for primary vaccination. However, after booster immunization, memory B-cell responses were effectively regulated through extrafollicular mechanisms, independent of TFH cells. Ablating IL-4 receptor signaling in B cells attenuated antibody production in both the primary and memory phases, highlighting the critical role of IL-4 for optimal humoral immunity. We identified a unique population of IL-4-expressing memory T (IL-4+Tm) cells, characterized by CD27, GATA3, and IRF4 expression, that is strongly associated with these extrafollicular memory B-cell responses, capable of neutralizing SARS-CoV-2 variants. Furthermore, Omicron-based booster immunization recovered the immunity against emerging variants under TFH-deficient conditions. These results suggest that IL-4+Tm cells are an alternative pathway to sustain memory responses when GC function is impaired, particularly in immunocompromised states. Our study advances the understanding of memory T-cell-mediated humoral responses to SARS-CoV-2, offering insights for future vaccine strategies.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"41-55"},"PeriodicalIF":3.4,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952896","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

Correction to: SLAMF6 regulates basal T cell receptor signaling and influences invariant natural killer T cell lineage diversity. 修正：SLAMF6调节基础T细胞受体信号传导并影响不变的自然杀伤T细胞谱系多样性。

IF 3.4 4区医学

International immunology Pub Date : 2026-01-14 DOI: 10.1093/intimm/dxaf064

引用次数: 0