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A Metabolite-Triggered Tuft Cell-ILC2 Circuit Drives Small Intestinal Remodeling.
Cell ( IF 45.5 ) Pub Date : 2018-Jul-12 , DOI: 10.1016/j.cell.2018.05.014
Christoph Schneider 1 , Claire E O'Leary 1 , Jakob von Moltke 1 , Hong-Erh Liang 1 , Qi Yan Ang 2 , Peter J Turnbaugh 2 , Sridhar Radhakrishnan 3 , Michael Pellizzon 3 , Averil Ma 1 , Richard M Locksley 4
Cell ( IF 45.5 ) Pub Date : 2018-Jul-12 , DOI: 10.1016/j.cell.2018.05.014
Christoph Schneider 1 , Claire E O'Leary 1 , Jakob von Moltke 1 , Hong-Erh Liang 1 , Qi Yan Ang 2 , Peter J Turnbaugh 2 , Sridhar Radhakrishnan 3 , Michael Pellizzon 3 , Averil Ma 1 , Richard M Locksley 4
Affiliation
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The small intestinal tuft cell-ILC2 circuit mediates epithelial responses to intestinal helminths and protists by tuft cell chemosensory-like sensing and IL-25-mediated activation of lamina propria ILC2s. Small intestine ILC2s constitutively express the IL-25 receptor, which is negatively regulated by A20 (Tnfaip3). A20 deficiency in ILC2s spontaneously triggers the circuit and, unexpectedly, promotes adaptive small-intestinal lengthening and remodeling. Circuit activation occurs upon weaning and is enabled by dietary polysaccharides that render mice permissive for Tritrichomonas colonization, resulting in luminal accumulation of acetate and succinate, metabolites of the protist hydrogenosome. Tuft cells express GPR91, the succinate receptor, and dietary succinate, but not acetate, activates ILC2s via a tuft-, TRPM5-, and IL-25-dependent pathway. Also induced by parasitic helminths, circuit activation and small intestinal remodeling impairs infestation by new helminths, consistent with the phenomenon of concomitant immunity. We describe a metabolic sensing circuit that may have evolved to facilitate mutualistic responses to luminal pathosymbionts.
中文翻译：
代谢物触发的簇绒细胞-ILC2 电路驱动小肠重塑。
小肠簇状细胞-ILC2 回路通过簇状细胞化学感应样传感和 IL-25 介导的固有层 ILC2 激活介导上皮对肠道蠕虫和原生生物的反应。小肠 ILC2 组成型表达受 A20 (Tnfaip3) 负调控的 IL-25 受体。ILC2s 中的 A20 缺乏会自发触发回路，并出乎意料地促进适应性小肠延长和重塑。回路激活在断奶时发生，并由膳食多糖启用，使小鼠允许毛滴虫定殖，导致腔内积聚乙酸和琥珀酸，即原生生物氢糖体的代谢物。簇绒细胞表达 GPR91（琥珀酸盐受体）和膳食琥珀酸盐（而非乙酸盐）通过簇绒、TRPM5 和 IL-25 依赖性途径激活 ILC2。同样由寄生蠕虫诱导，电路激活和小肠重塑削弱了新蠕虫的侵染，与伴随免疫现象一致。我们描述了一种代谢传感电路，该电路可能已经进化以促进对腔内病理共生体的共生反应。
更新日期：2018-06-07
中文翻译：
代谢物触发的簇绒细胞-ILC2 电路驱动小肠重塑。
小肠簇状细胞-ILC2 回路通过簇状细胞化学感应样传感和 IL-25 介导的固有层 ILC2 激活介导上皮对肠道蠕虫和原生生物的反应。小肠 ILC2 组成型表达受 A20 (Tnfaip3) 负调控的 IL-25 受体。ILC2s 中的 A20 缺乏会自发触发回路，并出乎意料地促进适应性小肠延长和重塑。回路激活在断奶时发生，并由膳食多糖启用，使小鼠允许毛滴虫定殖，导致腔内积聚乙酸和琥珀酸，即原生生物氢糖体的代谢物。簇绒细胞表达 GPR91（琥珀酸盐受体）和膳食琥珀酸盐（而非乙酸盐）通过簇绒、TRPM5 和 IL-25 依赖性途径激活 ILC2。同样由寄生蠕虫诱导，电路激活和小肠重塑削弱了新蠕虫的侵染，与伴随免疫现象一致。我们描述了一种代谢传感电路，该电路可能已经进化以促进对腔内病理共生体的共生反应。
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