Journal of immunology最新文献_第3页

HIV-1 broadly neutralizing antibodies demonstrate a high propensity for binding to heme. HIV-1广泛中和抗体显示出与血红素结合的高倾向。

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-03-22 DOI: 10.1093/jimmun/vkaf015

Robin V Lacombe, Valérie Lorin, Cyril Planchais, Tin Hinan Lassouani, Eline Haerens, Maxime Lecerf, Sébastien Lacroix-Desmazes, Hugo Mouquet, Jordan D Dimitrov

{"title":"HIV-1 broadly neutralizing antibodies demonstrate a high propensity for binding to heme.","authors":"Robin V Lacombe, Valérie Lorin, Cyril Planchais, Tin Hinan Lassouani, Eline Haerens, Maxime Lecerf, Sébastien Lacroix-Desmazes, Hugo Mouquet, Jordan D Dimitrov","doi":"10.1093/jimmun/vkaf015","DOIUrl":"https://doi.org/10.1093/jimmun/vkaf015","url":null,"abstract":"Polyreactivity is the ability of antibodies to bind to various unrelated antigens with low affinities and is a frequent feature of HIV-1 broadly neutralizing antibodies (bNAbs). Besides naturally occurring polyreactivity, human immune repertoires contain antibodies that can acquire polyreactivity de novo, by their interaction with the heterocyclic cofactor molecule heme. Since polyreactivity could influence antibody functions, we investigated here the impact of cofactor-induced polyreactivity on HIV-1 bNAbs. To this end, we evaluated the binding to heme of 38 HIV-1 bNAbs and 43 influenza virus (Flu) neutralizing antibodies. The majority of HIV-1 bNAbs were heme reactive, whereas only few human anti-Flu antibodies interacted with this cofactor. Molecular modeling and mutagenesis further showed that heme interacts with regions rich in aromatic and positively charged amino acid residues in bNAbs' paratopes. Strikingly, heme interaction with bNAbs strongly enhanced their intrinsic polyreactivity, while not altering their HIV-1 binding and neutralization potentials. Together, these findings contribute to a better understanding of the molecular properties of HIV-1-neutralizing Abs and underscore the importance of the interaction of bNAbs with heme under certain pathological conditions.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

High-salt diet drives depression-like behavior in mice by inducing IL-17A production. 高盐饮食通过诱导IL-17A的产生来驱动小鼠的抑郁样行为。

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-03-22 DOI: 10.1093/jimmun/vkaf019

Di Lu, Wenjie Chen, Wenhui Sun, Chuan Wei, Xuan Xie, Na Li, Haiyan Yan, Ying Chen, Yue Wu, Zhigang Lei, Lei Xu, Jifeng Zhu, Yalin Li, Chuan Su, Wei Li, Sha Zhou, Xiaojun Chen

引用次数: 0

A novel TOX-nanoluciferase reporter mouse for exploring modulators of T cell exhaustion. 用于探索 T 细胞衰竭调节剂的新型 TOX 核荧光素酶报告小鼠

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-03-22 DOI: 10.1093/jimmun/vkaf009

Ling Li, Yvonne M Mueller, Kou Hioki, Renske J H den Dekker, Inge Brouwers-Haspels, Laura Mezzanotte, Alex Maas, Stefan Erkeland, Peter D Katsikis

{"title":"A novel TOX-nanoluciferase reporter mouse for exploring modulators of T cell exhaustion.","authors":"Ling Li, Yvonne M Mueller, Kou Hioki, Renske J H den Dekker, Inge Brouwers-Haspels, Laura Mezzanotte, Alex Maas, Stefan Erkeland, Peter D Katsikis","doi":"10.1093/jimmun/vkaf009","DOIUrl":"https://doi.org/10.1093/jimmun/vkaf009","url":null,"abstract":"Cytotoxic T cell (CTL) exhaustion is driven by chronic T cell receptor (TCR) stimulation, leading to a dysfunctional state of cells. Exhausted CTLs exhibit diminished effector function against chronic infections and cancers. Therefore, reducing CTL exhaustion may re-establish effective adaptive immune responses. One feature of exhausted CTLs is the sustained and stable expression of transcription factor thymocyte selection-associated high mobility group box (TOX). Downregulating TOX expression in CD8+ T cells enhances their antitumor activities and improves immune checkpoint blockade (ICB) efficiency. We generated a reporter transgenic mouse to rapidly detect the expression of TOX by measuring luciferase activity. We knocked in a reporter cassette containing NanoLuc bioluminescent luciferase (Nluc) into the Tox gene locus by CRISPR/Cas9 (Tox-NLuc mice). We further generated Tox-NLuc-OT-I mice by crossing Tox-NLuc mice with OT-I mice, which allows the induction of CTL exhaustion in vitro by repeated stimulation of CD8+ T cells with OVA (257-264) peptide. Luciferase assays showed that higher luminescent signals were detected in exhausted CTLs compared to non-exhausted CTLs, which can be visualized by bioluminescence imaging. Bioluminescence changes were confirmed by measuring TOX expression by flow cytometry. The luminescence in exhausted CTLs decreased significantly when cells treated with ibrutinib and bryostatin-1, drugs that were found to directly modulate T cell exhaustion and decrease TOX expression. In summary, we have developed a novel TOX-nanoluciferase-based reporter system that can be used to monitor TOX expression and may facilitate the screening of molecules that modulate CTL exhaustion.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

DHODH inhibition alters T cell metabolism limiting acute graft-versus-host disease while retaining graft-versus-leukemia response. DHODH抑制改变T细胞代谢，限制急性移植物抗宿主病，同时保持移植物抗白血病反应。

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-03-22 DOI: 10.1093/jimmun/vkaf023

Rathan Kumar, Kara M Braunreiter, Lotus Neidemire-Colley, Natalie Sell, Yandi Gao, Camryn Steere, Margot Weber, Dhruva Vanakeri, Eunice Choi, Hannah K Choe, Sandip Vibhute, Chad Bennett, Craig A Byersdorfer, Ola A Elgamal, Thomas E Goodwin, Erin K Hertlein, John C Byrd, Parvathi Ranganathan

{"title":"DHODH inhibition alters T cell metabolism limiting acute graft-versus-host disease while retaining graft-versus-leukemia response.","authors":"Rathan Kumar, Kara M Braunreiter, Lotus Neidemire-Colley, Natalie Sell, Yandi Gao, Camryn Steere, Margot Weber, Dhruva Vanakeri, Eunice Choi, Hannah K Choe, Sandip Vibhute, Chad Bennett, Craig A Byersdorfer, Ola A Elgamal, Thomas E Goodwin, Erin K Hertlein, John C Byrd, Parvathi Ranganathan","doi":"10.1093/jimmun/vkaf023","DOIUrl":"10.1093/jimmun/vkaf023","url":null,"abstract":"Acute graft-versus-host disease (GVHD) is a donor T cell driven complication and the leading cause of non-relapse mortality in patients receiving an allogeneic hematopoietic cell transplantation (allo-HCT). Allogeneic donor T cells eradicate residual leukemia and prevent relapse via the graft-versus-leukemia (GVL) effect and are critical for responding against opportunistic infections post-transplant. Current regimens successful in preventing GVHD are broadly immunosuppressive and come at the cost of increased risk of relapse and/or infection. Therefore, there is an urgent need for new approaches that limit GVHD while retaining GVL responses. During GVHD, alloreactive T cells boost their energy production through oxidative phosphorylation (OXPHOS) and glycolysis, supporting heightened proliferation and pathogenicity against healthy host tissues. The enzyme dihydroorate dehydrogenase (DHODH), is essential for de novo pyrimidine biosynthesis and for maintaining mitochondrial membrane potential during OXPHOS. Having shown upregulation of DHODH messenger RNA and protein expression in activated human T cells, we evaluated DHODH inhibition, via a small molecule inhibitor HOSU-53, as a therapeutic approach for GVHD. Inhibiting DHODH significantly reduced oxidative metabolism in T cells both during and after activation, while selectively suppressing inflammatory cytokine production in de novo activated, but not previously activated, T cells. In a xenogeneic model, HOSU-53 treatment limited GVHD severity, decreased pathogenic Th1 and Th17 response, and preserved beneficial GVL effects. Altogether, we identify DHODH inhibition as an innovative treatment strategy in allo-HCT recipients to reduce GVHD severity and retain effective GVL response.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Galectin-3 regulates erythropoiesis and enhances the immunoregulatory properties of CD71+ erythroid cells across developmental stages. 半乳糖凝集素-3调节红细胞生成并增强CD71+红细胞在发育阶段的免疫调节特性。

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-03-22 DOI: 10.1093/jimmun/vkaf020

Shokrollah Elahi, Zahra Elahi, Najmeh Bozorgmehr, Eliana Perez Rosero, Amirhossein Rahmati, Amal Abouda

{"title":"Galectin-3 regulates erythropoiesis and enhances the immunoregulatory properties of CD71+ erythroid cells across developmental stages.","authors":"Shokrollah Elahi, Zahra Elahi, Najmeh Bozorgmehr, Eliana Perez Rosero, Amirhossein Rahmati, Amal Abouda","doi":"10.1093/jimmun/vkaf020","DOIUrl":"https://doi.org/10.1093/jimmun/vkaf020","url":null,"abstract":"Galectins are expressed by different immune and nonimmune cells with diverse immunomodulatory properties. However, their roles in erythropoiesis remain unknown. We investigated the expression of galectin genes in splenic CD71+ erythroid cells (CECs) from neonatal BALB/c mice at various developmental stages using bulk RNA sequencing. Our analysis revealed distinct gene expression profiles at different ages. Specifically, CECs from day-3 mice had a markedly different expression pattern compared to those from days 6, 12, and 28. Notably, Lgals1, Lgals3, Lgals4, Lgals8, and Lgals9 were constitutively expressed in CECs, with galectin-3 (Gal-3) showing predominant surface expression, unlike Gal-1 and Gal-9. Further analysis revealed that Gal-3+ CECs exhibited elevated levels of TGF-β, ROS, arginase I, VISTA, and PD-L1, correlating with enhanced immunosuppressive functions. These cells also demonstrated increased CD45, c-kit, Ki67, and p21 levels, indicating heightened proliferative activity despite showing increased apoptosis. Moreover, we found that Gal-3+ CECs displayed enhanced activation of signaling pathways, including STAT5, MAPK, and LCK. Additionally, Gal-3+ CECs co-expressed Fas and FasL, implicating these molecules in the regulation of early erythroblasts. Notably, Gal-3 interacted with CD71 and GARP, influencing CECs' immunoregulatory roles. In tissue-specific studies, we found varying frequencies of Gal-3+ CECs across the spleen, liver, and bone marrow (BM), with notable variations in the placenta and fetal liver. These results were paralleled in human BM-derived CECs, which also exhibited high Gal-3 levels. Our findings emphasize the critical role of Gal-3 in modulating erythropoiesis and suggest that Gal-3+ CECs possess enhanced immunoregulatory capacities.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Zebrafish hif1β attenuates antiviral innate immunity by suppressing Irf7 transcriptional activity. 斑马鱼hf1 β通过抑制Irf7转录活性减弱抗病毒先天免疫。

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-03-21 DOI: 10.1093/jimmun/vkaf018

Le Yuan, Gang Ouyang, Qian Liao, Yanan Song, Yanyi Wang, Ziyi Li, Zhi Li, Jun Li, Jing Wang, Wuhan Xiao

引用次数: 0

Can autoimmune disease be cured by deep CD19+ cell depletion? 深度消耗 CD19+ 细胞能治愈自身免疫性疾病吗？

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-03-21 DOI: 10.1093/jimmun/vkaf008

Dan Suan, John Moore, Christopher C Goodnow

{"title":"Can autoimmune disease be cured by deep CD19+ cell depletion?","authors":"Dan Suan, John Moore, Christopher C Goodnow","doi":"10.1093/jimmun/vkaf008","DOIUrl":"https://doi.org/10.1093/jimmun/vkaf008","url":null,"abstract":"Therapeutic B cell depletion with monoclonal antibodies targeting CD20 forced a rethink about the pathogenic role of B cells and plasma cells in autoimmune diseases; however, it was tempered by frequent clinical relapses or nonresponse to CD20-directed therapy. Here, we re-evaluate B cell depletion strategies in autoimmunity prompted by 4 recent advances. The first is analysis of clonal accumulations of CD20- CD19+ plasma cells making autoantibodies in patients with anti-CD20 refractory autoimmune disease. The second is the remarkable clinical remissions induced by anti-CD19 chimeric antigen receptor T cells in cases of anti-CD20 refractory autoimmunity. The third is evidence that CD19+ plasma cells comprise the majority of plasma cells in humans, are not terminally differentiated, are long-lived, and if self-reactive have potent capacity to capture autoantigens via their surface immunoglobulin and present major histocompatibility complex class II-bound peptides. The fourth is the role of autoantigen-binding B cells and CD19+ plasma cells as key antigen-presenting cells in \"T cell-mediated\" autoimmune disorders, type 1 diabetes and celiac disease. Viewing human memory B cells and plasma cells from this alternative perspective offers an explanation for why deep CD19 compartmental depletion may be effective at achieving complete and durable remissions in the autoantibody-positive autoimmune diseases as a group, irrespective of whether the autoantibody is pathogenic.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Differential expression of S100A10 protein in leukocytes and its effects on monocyte emigration from bone marrow. S100A10蛋白在白细胞中的差异表达及其对骨髓单核细胞迁移的影响。

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-03-20 DOI: 10.1093/jimmun/vkaf021

Yuxin Zhao, Shan Jiang, Yang Lv, Jingtao Gao, Lichen Zhang, Xueqin Tian, Xiaohang Sheng, Han Wang, Cun Guo, Wei Lu, Chuang Li, Tingmin Chang, Yunwei Lou, Hui Wang

{"title":"Differential expression of S100A10 protein in leukocytes and its effects on monocyte emigration from bone marrow.","authors":"Yuxin Zhao, Shan Jiang, Yang Lv, Jingtao Gao, Lichen Zhang, Xueqin Tian, Xiaohang Sheng, Han Wang, Cun Guo, Wei Lu, Chuang Li, Tingmin Chang, Yunwei Lou, Hui Wang","doi":"10.1093/jimmun/vkaf021","DOIUrl":"https://doi.org/10.1093/jimmun/vkaf021","url":null,"abstract":"Although the importance of the unique member of S100 EF-hand family, S100A10 in health and disease is well appreciated, a precise characterization of S100A10 expression still remains elusive. To this purpose, we generated a knock-in mouse line in which downstream of the coding sequence of the S100a10 gene was inserted IRES-mCherry-pA sequence. Interestingly, mCherry fluorescence was widely distributed in splenic myeloid and lymphoid cells, whereas neutrophils showed a negligible mCherry level. By taking advantage of these reporter mice, we found Ly6C+ monocytes expressed the highest levels of S100A10 and bound significantly more plasminogen compared with the other respective leukocyte subsets. Furthermore, we demonstrated that S100A10 was required for emigration of Ly6C+ monocytes from bone marrow by mainly affecting CCR2 cell surface presentation. S100a10-/- mice had fewer circulating Ly6C+ monocytes and, after challenged with thioglycolate, accumulated less CCR2+ monocytes in bone marrow. However, S100A10 was not necessary for efficient neutrophil recruitment from the blood to inflamed tissue. These findings provide evidence that S100A10 is critical for monocyte mobilization and suggest its differential regulatory roles for monocyte and neutrophil chemoattractants in leukocyte homeostasis. Thus, targeting the S100A10-CCR2 pathway may be an attractive approach to regulate inflammatory responses and infectious diseases.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Exacerbated endoplasmic reticulum stress transmitted by endometrial stromal cells alters the conditioning of tolerogenic dendritic cells affecting trophoblast migration. 内膜基质细胞传递的内质网应激加剧，改变了影响滋养细胞迁移的耐受性树突状细胞的调节。

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-03-20 DOI: 10.1093/jimmun/vkae065

Elizabeth Soczewski, Ana Schafir, Lara Castagnola, Lourdes Materazzi, Laura Fernández, Agustina Marcial, Jessica Presa, Flavia Saravia, Esteban Grasso, Daiana Vota, Claudia Pérez Leirós, Rosanna Ramhorst, Soledad Gori

{"title":"Exacerbated endoplasmic reticulum stress transmitted by endometrial stromal cells alters the conditioning of tolerogenic dendritic cells affecting trophoblast migration.","authors":"Elizabeth Soczewski, Ana Schafir, Lara Castagnola, Lourdes Materazzi, Laura Fernández, Agustina Marcial, Jessica Presa, Flavia Saravia, Esteban Grasso, Daiana Vota, Claudia Pérez Leirós, Rosanna Ramhorst, Soledad Gori","doi":"10.1093/jimmun/vkae065","DOIUrl":"https://doi.org/10.1093/jimmun/vkae065","url":null,"abstract":"Endometrial stromal cells acquire a secretory profile associated with endoplasmic reticulum stress (ERS) and unfolded protein response (UPR) related to the onset of a sterile inflammatory response essential for sustaining embryo implantation. However, exacerbated stromal ERS/UPR is associated with reproductive complications. Given the ability of dendritic cells (DCs) to sense stress signals and be conditioned by stromal cells, here we investigated the transmission of ERS (TERS) from stromal cells to monocytes and its impact on tolerogenic DCs conditioning. Blood monocytes were differentiated into DCs (rhGM-CSF+rhIL-4, 5 d) in the presence or absence of conditioned media derived from either thapsigargin-treated (stressed) or nonstressed human endometrial stromal cell line. Soluble factors released by stressed stromal cells impaired CD1a+CD14- DC differentiation and induced a proinflammatory profile, increasing the CD86high cell population, COX-2 expression, and tumor necrosis factor (TNF)-α, interleukin (IL)-8 and IL-1β secretion. Additionally, TERS was observed in these cultures, with increased expression of IRE1α, PERK, and ATF4. Even the splicing of the adaptive UPR marker XBP1 was increased though at low levels, its nuclear translocation was unchanged. These effects on spliced XBP1, coupled with a decreased GRP78/BiP and heightened CHOP expression, suggest the triggering of terminal UPR over adaptive UPR, confirmed by the induction of lytic cell death in stressed cultures. Finally, exacerbated TERS negatively impacted trophoblast migration in a blastocyst-like spheroid in vitro model. These findings suggest that exacerbated stromal ERS can be transmitted to monocytes, altering their differentiation, immune profile, and viability, which could ultimately impair trophoblast migration.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

IL-7Rα signaling in regulatory T cells of adipose tissue is essential for systemic glucose homeostasis. 脂肪组织调节性T细胞中的IL-7Rα信号对于全身葡萄糖稳态至关重要。

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-03-19 DOI: 10.1093/jimmun/vkae064

Shizue Tani-Ichi, Shinya Abe, Hitoshi Miyachi, Satsuki Kitano, Akihiro Shimba, Aki Ejima, Takahiro Hara, Guangwei Cui, Tomonobu Kado, Shohei Hori, Kazuyuki Tobe, Koichi Ikuta

{"title":"IL-7Rα signaling in regulatory T cells of adipose tissue is essential for systemic glucose homeostasis.","authors":"Shizue Tani-Ichi, Shinya Abe, Hitoshi Miyachi, Satsuki Kitano, Akihiro Shimba, Aki Ejima, Takahiro Hara, Guangwei Cui, Tomonobu Kado, Shohei Hori, Kazuyuki Tobe, Koichi Ikuta","doi":"10.1093/jimmun/vkae064","DOIUrl":"https://doi.org/10.1093/jimmun/vkae064","url":null,"abstract":"Regulatory T cells (Tregs) mediate tissue homeostasis and repair. The function of the interleukin-7 receptor α (IL-7Rα) in nonlymphoid tissue Tregs is still unknown, although low expression of IL-7Rα is a widely accepted marker for Tregs. Here, we show that IL-33R (ST2)-expressing Tregs in the visceral adipose tissue (VAT) express the IL-7Rα at high levels. Treg-specific IL-7Rα-deficient mice exhibited reduced adipose ST2+ Tregs and impaired glucose tolerance, whereas IL-7Rα was dispensable for Tregs in lymphoid tissues. Mice deficient in thymic stromal lymphopoietin (TSLP), an additional ligand for IL-7Rα, displayed a modest decrease in adipose ST2+ Tregs and a reduced accumulation of adipose eosinophils, accompanied by slightly impaired glucose tolerance. In the VAT, mesothelial cells expressed IL-7, whereas adipose stem cells and folate receptor β-expressing tissue-resident macrophages expressed TSLP. Thus, this study indicates the significance of IL-7Rα signaling in the maintenance of VAT Tregs and glucose homeostasis, revealing a novel role for IL-7 and TSLP in immunometabolism.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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