The CD4(+) T cell response to a commensal-derived epitope transitions from a tolerant to an inflammatory state in Crohn's disease.
The CD4(+) T cell response to a commensal-derived epitope transitions from a tolerant to an inflammatory state in Crohn's disease.
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DOI：
10.1016/j.immuni.2022.08.016
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发表时间：
2022-10-11
期刊：
影响因子：
32.4
通讯作者：
Graham, Daniel B.
中科院分区：
文献类型：
--
作者：
Pedersen, Thomas K.;Brown, Eric M.;Plichta, Damian R.;Johansen, Joachim;Twardus, Shaina W.;Delorey, Toni M.;Lau, Helena;Vlamakis, Hera;Moon, James J.;Xavier, Ramnik J.;Graham, Daniel B.
宿主T辅助细胞和肠道微生物群之间的相互作用加强局部免疫耐受并调节肠外免疫。然而，我们对微生物组的抗原特异性耐受性的理解是有限的。在这里，我们开发了一种系统的方法来预测HLA II类特异性表位使用人源化细菌起源的T细胞抗原（hBOTA）算法。我们确定了一组不同的微生物组表位，跨越所有主要分类群，与多个HLA-II等位基因的呈递相容。特别是，我们发现了一个免疫显性表位从TonB依赖性受体SusC是普遍公认的和普遍存在的类杆菌。在健康人受试者中，SusC反应性T细胞应答的特征在于IL-10主导的细胞因子谱，而在活动性克罗恩病患者中，应答与升高的IL-17 A相关。我们的研究结果强调了微生物组中靶向抗原发现的潜力，以揭示炎症期间耐受和功能转变的原则。对肠道微生物组耐受的功能基础尚未完全了解。Pedersen等人开发了一种抗原发现方法来评估健康和炎症中微生物导向的T细胞免疫。它们揭示了T细胞介导的对肠道类杆菌的反应的动态性质，突出了克罗恩病中的炎症相关变化。
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. The functional basis of tolerance to the gut microbiome is incompletely understood. Pedersen et al. develop an antigen-discovery approach to assess microbiota-directed T cell immunity in health and inflammation. They reveal the dynamic nature of T cell-mediated responses toward commensal Bacteroidales, highlighting inflammation-associated changes in Crohn’s disease.
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影响因子：
6.4
作者：
Elhenawy W;Debelyy MO;Feldman MF
通讯作者：
Feldman MF
影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
DOI：
10.1093/bioinformatics/bts565
发表时间：
2012-12-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Fu L;Niu B;Zhu Z;Wu S;Li W
通讯作者：
Li W
影响因子：
3.7
作者：
Blanvillain S;Meyer D;Boulanger A;Lautier M;Guynet C;Denancé N;Vasse J;Lauber E;Arlat M
通讯作者：
Arlat M
影响因子：
32.4
作者：
Abelin, Jennifer G.;Harjanto, Dewi;Rooney, Michael S.
通讯作者：
Rooney, Michael S.