小柯机器人

美国麻省理工学院和哈佛大学布罗德研究所Daniel B. Graham和Ramnik J. Xavier共同合作近期取得重要工作进展，他们研究发现在克罗恩病中，CD4⁺ T细胞对共生体来源表位的反应从耐受状态过渡到炎症状态。该项研究成果2022年9月16日在线发表于《免疫学》杂志上。

研究人员开发了一种使用人源化细菌来源的T细胞抗原（hBOTA）算法来预测HLA II类特异性表位的系统方法。它们鉴定出了一组多样化的微生物组表位，涵盖所有主要分类群，与多个HLA-II等位基因的呈递相兼容。研究人员从TonB依赖性受体SusC中发现了一个免疫优势表位，该表位在类杆菌中被普遍认可且无处不在。在健康人类受试者中，SusC反应性T细胞应答的特征是IL-10主导的细胞因子谱，而在活动性克罗恩病患者中，反应与升高的IL-17A相关。他们的结果强调了在微生物组内发现靶向抗原的潜力，以揭示炎症期间的耐受性和功能转换的原则。

据介绍，宿主T辅助细胞和肠道菌群之间的相互作用加强了局部免疫耐受并调节了肠外免疫。然而，目前对于肠道菌群抗原特异性耐受的了解是有限的。

附：英文原文

Title: The CD4+ T cell response to a commensal-derived epitope transitions from a tolerant to an inflammatory state in Crohn’s disease

Author: Thomas K. Pedersen, Eric M. Brown, Damian R. Plichta, Joachim Johansen, Shaina W. Twardus, Toni M. Delorey, Helena Lau, Hera Vlamakis, James J. Moon, Ramnik J. Xavier, Daniel B. Graham

Issue&Volume: 2022-09-16

Abstract: Reciprocal interactions between host T helper cells and gut microbiota enforce local immunological tolerance and modulate extra-intestinal immunity. However, our understanding of antigen-specific tolerance to the microbiome is limited. Here, we developed a systematic approach to predict HLA class-II-specific epitopes using the humanized bacteria-originated T cell antigen (hBOTA) algorithm. We identified a diverse set of microbiome epitopes spanning all major taxa that are compatible with presentation by multiple HLA-II alleles. In particular, we uncovered an immunodominant epitope from the TonB-dependent receptor SusC that was universally recognized and ubiquitous among Bacteroidales. In healthy human subjects, SusC-reactive T cell responses were characterized by IL-10-dominant cytokine profiles, whereas in patients with active Crohn’s disease, responses were associated with elevated IL-17A. Our results highlight the potential of targeted antigen discovery within the microbiome to reveal principles of tolerance and functional transitions during inflammation.

DOI: 10.1016/j.immuni.2022.08.016

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00410-1

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