A hierarchy of intestinal antigens instructs the CD4+ T cell receptor repertoire

IF 25.5 1区 医学 Q1 IMMUNOLOGY
Jaeu Yi, Jisun Jung, David Horton, Patricia Hsieh, Yangqing Peng, Sean J. Wang, Rodney Newberry, Aaron C. Ericsson, Kwang Soon Kim, Andrew L. Kau, Chyi-Song Hsieh
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引用次数: 0

Abstract

Intestinal CD4+ T cells that are specific for self-, diet-, or commensal-derived antigens are critical for host tolerance but must also be tightly regulated to prevent aberrant activation and conditions like inflammatory bowel disease (IBD). However, it is unclear how the antigen source and location dictate the intestinal TCR repertoire. Here, we hierarchically classified self-, diet-, or microbiota-dependent TCRs using TCliβ TCRβ transgenic mice. This demonstrated that microbiota had a greater influence than diet on CD4+ T cell responses throughout the intestine at homeostasis. Complex bi-directional interactions between microbes and diet were also observed. In the context of murine colitis as a model of IBD, we showed that antigen-free diet substantially altered the microbiota and associated T cell responses, which ameliorated intestinal inflammation. Collectively, these findings suggest how deconvoluting the gut immune interactome may facilitate identifying primary microbial and dietary drivers of T cell responses during health and disease.
肠道抗原的层次结构指导CD4+ T细胞受体库
肠道CD4+ T细胞对自身、饮食或共生源性抗原具有特异性,对宿主耐受至关重要,但也必须严格调节,以防止异常激活和炎症性肠病(IBD)等疾病。然而,目前尚不清楚抗原来源和位置如何决定肠道TCR库。在这里,我们使用TCRβ转基因小鼠对自我、饮食或微生物依赖的TCRs进行分层分类。这表明微生物群比饮食对整个肠道内稳态CD4+ T细胞反应的影响更大。微生物与饮食之间复杂的双向相互作用也被观察到。在将小鼠结肠炎作为IBD模型的背景下,我们发现无抗原饮食极大地改变了微生物群和相关的T细胞反应,从而改善了肠道炎症。总的来说,这些发现表明,解开肠道免疫相互作用组可能有助于识别健康和疾病期间T细胞反应的主要微生物和饮食驱动因素。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Immunity
Immunity 医学-免疫学
CiteScore
49.40
自引率
2.20%
发文量
205
审稿时长
6 months
期刊介绍: Immunity is a publication that focuses on publishing significant advancements in research related to immunology. We encourage the submission of studies that offer groundbreaking immunological discoveries, whether at the molecular, cellular, or whole organism level. Topics of interest encompass a wide range, such as cancer, infectious diseases, neuroimmunology, autoimmune diseases, allergies, mucosal immunity, metabolic diseases, and homeostasis.
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