Gut Helicobacter presentation by multiple dendritic cell subsets enables context-specific regulatory T cell generation.
Gut Helicobacter presentation by multiple dendritic cell subsets enables context-specific regulatory T cell generation.
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DOI：
10.7554/elife.54792
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发表时间：
2021-02-03
期刊：
影响因子：
7.7
通讯作者：
Hsieh CS
中科院分区：
文献类型：
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作者：
Russler-Germain EV;Yi J;Young S;Nutsch K;Wong HS;Ai TL;Chai JN;Durai V;Kaplan DH;Germain RN;Murphy KM;Hsieh CS
耐受性外周调节性T （pTreg）细胞的产生通常被认为涉及CD103+肠道树突状细胞（dc），但它们在共生反应性pTreg发育中的作用尚不清楚。利用两个幽门螺杆菌特异性T细胞受体（TCR）转基因小鼠系，我们发现来自结肠引流肠系膜淋巴结的CD103+和CD103 -迁移性dc在体外向T细胞呈递幽门螺杆菌抗原。在小鼠遗传模型中，体内大多数CD103+迁移dc的丢失不会影响幽门螺杆菌特异性pTreg细胞产生的频率，也不会引起剩余CD103 - dc的代偿性耐受性改变。相比之下，体内th1促进生态位的激活阻断了幽门螺杆菌特异性pTreg的产生。因此，这些数据表明DC介导的效应T细胞分化是“主导”的模型，需要所有DC亚群呈递抗原都允许pTreg细胞诱导以维持肠道耐受性。
Generation of tolerogenic peripheral regulatory T (pTreg) cells is commonly thought to involve CD103+ gut dendritic cells (DCs), yet their role in commensal-reactive pTreg development is unclear. Using two Helicobacter-specific T cell receptor (TCR) transgenic mouse lines, we found that both CD103+ and CD103– migratory, but not resident, DCs from the colon-draining mesenteric lymph node presented Helicobacter antigens to T cells ex vivo. Loss of most CD103+ migratory DCs in vivo using murine genetic models did not affect the frequency of Helicobacter-specific pTreg cell generation or induce compensatory tolerogenic changes in the remaining CD103– DCs. By contrast, activation in a Th1-promoting niche in vivo blocked Helicobacter-specific pTreg generation. Thus, these data suggest a model where DC-mediated effector T cell differentiation is ‘dominant’, necessitating that all DC subsets presenting antigen are permissive for pTreg cell induction to maintain gut tolerance.