International immunology最新文献

{"title":"Control of Mucociliary Clearance in Airway Host Defense.","authors":"Noriko Shinjyo, Masahiko Shigemura, Yasutaka Okabe","doi":"10.1093/intimm/dxag034","DOIUrl":"https://doi.org/10.1093/intimm/dxag034","url":null,"abstract":"<p><p>Respiratory infections remain a major threat to global health. To counter these insults, the respiratory system has evolved multilayered defense strategies that integrate anatomical and mechanical barriers with both innate and adaptive immune responses. Mucociliary clearance (MCC) serves as a cornerstone of airway host defense, whereby coordinated ciliary beating at the luminal surface of the airway epithelium drives the efficient removal of inhaled particles and pathogens. This process provides robust, broad-spectrum protection against both routine environmental exposures and emerging respiratory pathogens. In this Review, we summarize the current understanding of respiratory barrier function and defense strategies, with a particular emphasis on the immunological and metabolic mechanisms that regulate MCC. We further highlight the role of aldehyde dehydrogenases (ALDHs) in preventing ciliary damage and preserving MCC function, thereby conferring protection against environmental stress and respiratory infections.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148404523","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}

{"title":"Single-cell RNA-sequencing of myasthenia gravis reveals transcriptional heterogeneity and dysfunction of immune cell populations.","authors":"Qingjun Wu, Yingyu Guo, Liying Zhou, Yi Tian, Hanbo Yu, Ting Zhou, Siyuan Yin, Lihui Zou","doi":"10.1093/intimm/dxag010","DOIUrl":"10.1093/intimm/dxag010","url":null,"abstract":"<p><p>The purpose of this study was to explore the composition and function of immune cell subsets at the single-cell level in the thymus and peripheral blood of patients with myasthenia gravis (MG). A total of 9701 and 23 846 cells, respectively, originated from the peripheral blood and thymus samples of two MG patients, and 6930 cells from the peripheral blood of two gender- and age-matched healthy controls (HCs) were selected for single-cell RNA-sequencing. Uniform manifold approximation and projection (UMAP), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Monocle3, and Velcyto were performed to analyze the composition, molecular and functional properties, and developmental trajectory of immune cell subsets. Four major cell populations of T cells, B cells, myeloid cells, and natural killer cells were identified, as well as their 15 cell subpopulations. An absolute predominance of T cells was found in the thymus and peripheral blood of MG patients, and the proportions of memory B cells in both plasma and thymus showed an increasing trend while the number of naïve B cells demonstrated a decreasing trend in MG patients compared with HCs. Besides, the monocytes in the peripheral blood of MG patients had the strongest interactions with other cells. Furthermore, CXCL, GAS, and CD30 signaling pathways were more enriched within MG peripheral blood. Our research clarifies the cellular heterogeneity in the pathogenesis of MG and characterizes the immune microenvironment of thymic tissues in MG patients.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"454-465"},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13319860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147305186","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}

{"title":"Transduction of Batf family members provides distinct functions to mouse CD8+ T cells.","authors":"Kenta Kondo, Mina Kumode, Hiroki Satooka, Koji Terada, Yusuke Sano, Nobuhito Nitta, Daisuke Okuzaki, Kensuke Takada, Takako Hirata, Hidetaka Kosako, Akira Andoh, Makoto Murata, Yasutoshi Agata","doi":"10.1093/intimm/dxag009","DOIUrl":"10.1093/intimm/dxag009","url":null,"abstract":"<p><p>Members of the Batf family, including Batf, Batf2, and Batf3, play critical roles in various immune cell types. Several studies have suggested redundant functions, as they can compensate for each other's functions. Here, we show that transduction of Batf family members confers distinct functional characteristics on CD8+ T cells. Batf- and Batf2-transduced CD8+ T cells exhibited effector and memory-like phenotypes, respectively. Notably, Batf3-transduced CD8+ T cells showed both effector- and memory-like phenotypes in response to effector- and memory-associated cytokines, respectively, and superior anti-tumor activity in vivo among Batf family members. Our results demonstrated that each Batf family member has distinct functions in CD8+ T cells. These findings help us understand the roles of the Batf family members in CD8+ T cells and contribute to the development of optimized adoptive T cell therapies against cancer.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"432-453"},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146213402","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}

{"title":"Identification and characterization of CXCL13 producers in bone tissue in response to fasting.","authors":"Takuma Okawa, Motoyoshi Nagai, Shinya Fujita, Koichiro Suzuki, Kazuaki Nakata, Reina Miyajima, Hiroaki Shiratori, Seiga Komiyama, Daisuke Takahashi, Yuki I Kawamura, Taeko Dohi, Burkhard Ludewig, Keiyo Takubo, Koji Hase","doi":"10.1093/intimm/dxag005","DOIUrl":"10.1093/intimm/dxag005","url":null,"abstract":"<p><p>The bone tissue serves as a dynamic reservoir that accommodates diverse immune cell populations during low-energy states such as fasting. Energy restriction and reduced metabolism induce a transient migration of naïve B cells from Peyer's patches to the bone marrow in mice, a process driven by the upregulation of Cxcl13 expression within the bone niche. However, the specific cellular source of CXCL13 and the upstream signals regulating its expression remain undefined. Our analysis identified the lineage-negative fraction of the bone as the major source of CXCL13. Single-cell RNA sequencing of these cells further demonstrated that Cxcl13 was selectively expressed by osteogenic mesenchymal stromal cells (MSCs) during fasting. Consistently, immunofluorescence imaging showed an increased frequency of these CXCL13-producing cells under fasting conditions, primarily localized within the perivascular niche. Gene Ontology analysis of differentially expressed genes in these cells during fasting revealed enrichment of TGF-β and PPAR signaling. In line with this, pharmacological intervention in either the TGF-β or PPARγ signaling pathway significantly attenuated fasting-induced naïve B-cell migration and CXCL13 production in the bone. These results establish a mechanistic link between systemic metabolic cues and the bone marrow immune microenvironment. We propose that osteogenic MSCs play a vital role in orchestrating this trafficking program for naïve B cells, underscoring a dynamic crosstalk between the bone stromal cells and the immune system.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"418-431"},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13319862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146085715","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}

{"title":"Association between autoimmune diseases and the gut microbiome.","authors":"Yudai Hirano, Yoshihiko Tomofuji, Ryuya Edahiro, Toshihiro Kishikawa, Satoru Miyawaki, Yukinori Okada","doi":"10.1093/intimm/dxag013","DOIUrl":"10.1093/intimm/dxag013","url":null,"abstract":"<p><p>The gut microbiome has emerged as an important environmental factor in the pathogenesis of autoimmune diseases. Advances in high-throughput sequencing technologies have enabled comprehensive characterization of the gut microbiome, providing detailed insights into its composition and functional potential. These approaches have been widely applied in autoimmune disease research, revealing disease-associated alterations in the gut microbiome of patients with conditions such as rheumatoid arthritis and systemic lupus erythematosus. In addition, microbiome sequencing data can be leveraged to investigate the gut virome, including viruses residing in the intestinal ecosystem. This review summarizes current evidence linking autoimmune diseases and the gut microbiome, with a particular focus on studies employing microbiome sequencing-based analyses.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"409-417"},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147432637","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}

{"title":"Signaling and Transcriptional Control of Thymocyte Differentiation.","authors":"Ichiro Taniuchi","doi":"10.1093/intimm/dxag030","DOIUrl":"https://doi.org/10.1093/intimm/dxag030","url":null,"abstract":"<p><p>This review summarizes key topics discussed in the session \"Biology within the Thymus\" at the 54th Annual Meeting of the Japanese Society for Immunology, which highlighted recent advances in our understanding of T-cell development and fate determination. In particular, the session focused on transcriptional regulation of T-lineage commitment and the mechanisms by which T-cell receptor (SP) signaling governs thymocyte differentiation. Early T-lineage commitment is established through the integration of thymic microenvironmental cues and intrinsic transcription factors, including Bcl11b, PU.1, and Runx family proteins. Among these, Runx transcription factors play essential roles throughout thymocyte development, not primarily through changes in expression but through dynamic regulation of their molecular interactions and genomic occupancy. Following commitment, αβTCR-expressing CD4+CD8+ double-positive (DP) thymocytes undergo MHC-dependent selection and differentiate into CD4+ helper or CD8+ cytotoxic T cells. Although the core components of proximal TCR signaling are largely shared, accumulating observations suggest that qualitative and quantitative differences in signaling-shaped by signal strength, duration, and subcellular context-may contribute to lineage specification. In this regard, recent studies discussed in this session highlighted the role of co-receptor-free Lck as an active signaling pool capable of initiating TCR signaling independently of CD4 or CD8 association, thereby adding an additional layer of complexity to MHC-dependent thymic selection. In addition, post-translational modification of Runx proteins, particularly within the conserved WRPY motif, has emerged as a molecular link between proximal TCR signaling mediated by kinases such as Lck and lineage-specific transcriptional repression. Together with advances in thymic culture systems, genome editing, and proteomic approaches, these findings underscore the tight coupling between proximal TCR signaling-including both co-receptor-dependent and co-receptor-independent Lck activity-and transcriptional regulation, and highlight Runx transcription factors as key integrators that translate MHC-specific TCR signals into transcriptional programs determining thymocyte fate.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148156347","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}

{"title":"17,18-epoxyeicosatetraenoic acid and its metabolite attenuate IL-33-induced airway inflammation involving group 2 innate lymphoid cells.","authors":"Ichiro Tojima, Tatsuji Nishiguchi, Kento Kawakita, Yoshihito Kubo, Takuya Murao, Keigo Nakamura, Koji Matsumoto, Hideaki Kouzaki, Shino Shimizu, Takeshi Shimizu, Yukinori Takenaka","doi":"10.1093/intimm/dxag029","DOIUrl":"https://doi.org/10.1093/intimm/dxag029","url":null,"abstract":"<p><p>Group 2 innate lymphoid cells (ILC2s) play critical roles in type 2 airway inflammation. 17,18-epoxyeicosatetraenoic acid (17,18-EpETE), an eicosapentaenoic acid metabolite, is generated from dietary omega-3 fatty acids, and may have anti-inflammatory activities. We evaluated the effect of 17,18-EpETE and its metabolite, 17,18-dihydroxy-eicosa-5,8,11,14-tetraenoic acid (17,18-diHETE), on IL-33-induced airway inflammation involving ILC2s. We evaluated the in vitro effects of 17,18-EpETE and 17,18-diHETE on the IL-33-induced production of IL-5 and IL-13 by human ILC2s (isolated from peripheral blood) using ELISA. Expression of the corresponding fatty acid receptors and the GATA-3 transcription factor were examined using flow cytometry and quantitative RT-PCR. Additionally, we examined the in vivo effects of 17,18-EpETE or 17,18-diHETE in a mouse model of type 2 airway inflammation induced by intranasal (i.n.) instillation of IL-33. 17,18-EpETE or 17,18-diHETE inhibited IL-33-induced production of IL-5 and IL-13, and IL-33-induced expression of GATA-3 in human ILC2s. GW1100, an antagonist of G protein-coupled receptor (GPR) 40, or GW9662, an antagonist of peroxisome proliferator-activated receptor γ (PPARγ), counteracted the inhibitory effects of 17,18-EpETE or 17,18-diHETE on the IL-33-induced production of IL-5 and IL-13 by ILC2s. I.n. administration of 17,18-EpETE or 17,18-diHETE attenuated IL-33-induced eosinophil infiltration and mucus production in mouse nasal mucosa, and production of IL-5 and IL-13 in lung tissue and bronchoalveolar lavage fluid. The present study demonstrated the anti-inflammatory effects of 17,18-EpETE and 17,18-diHETE on IL-33-induced airway inflammation involving ILC2s. I.n. administration of 17,18-EpETE may be a new therapeutic approach for the treatment of intractable type 2 airway inflammation.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148149543","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}

{"title":"FcμR enhances recall responses by promoting the generation of CD80+PD-L2+ memory B cells.","authors":"Runyun Zhang, Jiping Sun, Lulu Dong, Ziying Hu, Qing Min, Ying Wang, Zichao Wen, Jingjing Zhao, Jue Wang, Jun Liu, Xiaoqian Feng, Yingying Luan, Xin Meng, Meiping Yu, Yaxuan Li, Chaoqun Cui, Chunhui Lu, Xuzhe Wu, Koji Hase, Yoshimasa Takahashi, Tomohiro Kurosaki, Ji-Yang Wang","doi":"10.1093/intimm/dxag028","DOIUrl":"https://doi.org/10.1093/intimm/dxag028","url":null,"abstract":"<p><p>The IgM Fc receptor (FcμR), the sole receptor specific for IgM, is crucial for B cell survival and humoral immunity. Yet, its role in memory B cells (MBCs) has remained unclear. Here, we show that FcμR-/- mice immunized with the T-dependent antigen 4-hydroxy-3-nitrophenyl acetyl-chicken γ-globulin (NP-CGG) generate normal numbers of IgG1+ MBCs with long-term survival comparable to that of WT mice. However, the IgG1+ MBCs in FcμR-/- mice contained a reduced proportion of mature CD80+PD-L2+ cells, a subset associated with potent recall responses and plasma cell differentiation. Consistently, adoptive transfer of NP-specific MBCs and CGG-specific memory T cells into Rag1-/- mice revealed significantly diminished memory B cell responses in recipients of FcμR-/- MBCs. Mechanistically, FcμR-/- IgG1+ MBCs exhibited impaired B cell receptor signaling and reduced activation of transcription factors essential for plasma cell differentiation upon antigen re-challenge both in vivo and in vitro. Together, these findings establish FcμR as a previously unrecognized key regulator of CD80+PD-L2+ MBC formation and recall responses.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148143346","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}

{"title":"Overexpression of the transcriptional corepressor Tle1 enhances effector proliferation of CD8+ T cells during acute and chronic viral infections.","authors":"Ryotaro Shiga, Sotaro Fujisawa, Yamato Tanabe, Junko Kurachi, Miki Koura, Toshikatsu Tamai, Makoto Kurachi","doi":"10.1093/intimm/dxag001","DOIUrl":"10.1093/intimm/dxag001","url":null,"abstract":"<p><p>The transcriptional corepressor Tle (transducin-like enhancer of split) proteins interact with transcription factors such as TCF-1 and Runx3 to regulate transcriptional programmes during cellular development and differentiation; however, their roles in CD8+ T cell differentiation, particularly under conditions of chronic antigen stimulation, remain poorly defined. Here, we demonstrated that overexpression of Tle1, Tle3, and Tle4 improves the proliferation of antigen-specific effector CD8+ T cells during both acute and chronic viral infections. Notably, overexpression of Tle3 and Tle4, but not Tle1, augmented secondary responses of memory CD8+ T cells in the context of acute viral infection. Tle1-overexpressing CD8+ T cells displayed enhanced TCR signal strength, accompanied by elevated expression of immunoinhibitory receptors such as PD-1 and LAG-3. Transcriptome analyses and genome-wide binding profiles suggested that Tle1 and Tle3 cooperate with multiple transcription factors, including members of the Ets, AP-1, and Runx families, to drive expression of genes involved in the activation and maintenance of antigen-specific CD8+ T cell responses. Notably, Tle1 overexpression improves cytotoxic T lymphocyte (CTL) responses to PD-1/PD-L1 blockade during chronic viral infection. Tle1 was found to enhance TCR signalling and the expression of immunoinhibitory receptors through repression of TCF-1, whereas its effect on effector CD8+ T cell proliferation occurred independently of TCF-1. These findings revealed the regulatory roles of Tle proteins in orchestrating transcription factor networks that govern CD8+ T cell differentiation during viral infections.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"357-370"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147432661","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}

{"title":"Heterogeneity of memory B cells in human blood.","authors":"David Priest, James Wing","doi":"10.1093/intimm/dxag006","DOIUrl":"10.1093/intimm/dxag006","url":null,"abstract":"<p><p>In human blood B cells exist in a variety of forms ranging from antigen-inexperienced naive cells to long-term memory cells, and antibody-producing plasma cells. Historically, the divisions between these types of cells have been defined by a few characteristic surface markers such as IgD, CD27, and CD21, but recent advances in single-cell techniques such as high-parameter cytometry and single-cell sequencing have revealed a greater diversity of populations. An expanding palette of markers has helped to better define B cell subsets but can be a source of confusion when overlapping cell types are identified using different sets of markers. In this review, we will discuss the conflicting and overlapping phenotypic and functional identities of human circulating B cells with a particular emphasis on memory B cells. We also propose a framework in which five B cell markers (IgD, CD27, CD21, CD11c, and a glycosylated isoform of CD45RB) can discriminate the majority of B cell populations in human blood.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"348-356"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146105386","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}