An IL-23R/IL-22 Circuit Regulates Epithelial Serum Amyloid A to Promote Local Effector Th17 Responses.
An IL-23R/IL-22 Circuit Regulates Epithelial Serum Amyloid A to Promote Local Effector Th17 Responses.
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DOI：
10.1016/j.cell.2015.08.061
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发表时间：
2015-10-08
期刊：
影响因子：
64.5
通讯作者：
Littman DR
中科院分区：
文献类型：
--
作者：
Sano T;Huang W;Hall JA;Yang Y;Chen A;Gavzy SJ;Lee JY;Ziel JW;Miraldi ER;Domingos AI;Bonneau R;Littman DR
RORγt+ Th17细胞对粘膜防御很重要，但也有助于自身免疫性疾病。它们在肠道中对微生物群做出反应，并产生IL-17细胞因子。分节丝状细菌（SFB）是th17诱导的共生体，可增强小鼠自身免疫。rr γ T + T细胞在SFB定殖后早期在肠系膜淋巴结内被诱导，并分布在胃肠道的不同节段。然而，IL-17A的产生仅限于回肠，在那里SFB与上皮直接接触并诱导血清淀粉样蛋白1和2 (SAA1/2)，从而促进RORγt+ T细胞中IL-17A的局部表达。我们确定了3型先天淋巴样细胞（ILC3）的sfb依赖性作用，其分泌IL-22以stat3依赖性方式诱导上皮SAA的产生。这突出了组织微环境在激活Th17细胞效应功能中的关键作用，这可能对这些细胞如何促进炎症性疾病具有重要意义。
RORγt+ Th17 cells are important for mucosal defenses, but also contribute to autoimmune disease. They accumulate in the intestine in response to microbiota and produce IL-17 cytokines. Segmented filamentous bacteria (SFB) are Th17-inducing commensals that potentiate autoimmunity in mice. RORγt+ T cells were induced in mesenteric lymph nodes early after SFB colonization and distributed across different segments of the gastrointestinal tract. However, robust IL-17A production was restricted to the ileum, where SFB makes direct contact with the epithelium and induces serum amyloid A proteins 1 and 2 (SAA1/2), which promote local IL-17A expression in RORγt+ T cells. We identified an SFB-dependent role of type 3 innate lymphoid cells (ILC3), which secreted IL-22 that induced epithelial SAA production in a Stat3-dependent manner. This highlights the critical role of tissue microenvironment in activating effector functions of committed Th17 cells, which may have important implications for how these cells contribute to inflammatory disease.