Yi Jaeu, Jung Jisun, Horton David, Hsieh Patricia, Peng Yangqing, Wang Sean J, Newberry Rodney, Ericsson Aaron C, Kim Kwang Soon, Kau Andrew L, Hsieh Chyi-Song
Department of Internal Medicine, Division of Rheumatology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Biological Science, Ajou University, Suwon 16499, Republic of Korea.
Department of Internal Medicine, Division of Rheumatology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Immunity. 2025 May 13;58(5):1217-1235.e4. doi: 10.1016/j.immuni.2025.04.011. Epub 2025 May 2.
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.
对自身、饮食或共生菌衍生抗原具有特异性的肠道CD4 T细胞对宿主耐受性至关重要，但也必须受到严格调控，以防止异常激活和诸如炎症性肠病（IBD）等病症。然而，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TCliβ TCRβ转基因小鼠对自身、饮食或微生物群依赖性TCR进行了分层分类。这表明，在稳态下，微生物群对整个肠道CD4 T细胞反应的影响大于饮食。还观察到微生物与饮食之间复杂的双向相互作用。在作为IBD模型的小鼠结肠炎背景下，我们表明无抗原饮食显著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。
