Epithelial cell specific Raptor is required for initiation of type 2 mucosal immunity in small intestine.
Epithelial cell specific Raptor is required for initiation of type 2 mucosal immunity in small intestine.
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DOI：
10.1038/s41598-017-06070-w
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发表时间：
2017-07-17
影响因子：
4.6
通讯作者：
Guo J
中科院分区：
文献类型：
--
作者：
Aladegbami B;Barron L;Bao J;Colasanti J;Erwin CR;Warner BW;Guo J
肠簇细胞是小肠中4种分泌细胞系之一，也是IL-25的来源，IL-25是针对寄生虫感染的2型免疫应答的关键启动物。他莫昔芬注射液在鼠毛单胞菌（Tritrichomonas muris, Tm）感染小鼠肠上皮中急性删除哺乳动物雷帕霉素靶蛋白1 （mTORC1）的关键支架蛋白Raptor后，绒毛细胞、上皮IL-25和间质IL-13明显减少，但不影响Tm负荷。当雷帕霉素处理Tm感染小鼠时，肠细胞中DCLK1和IL-25的表达以及间质中IL-13的表达均降低。大量小肠切除术后，由于术后饮食的影响，簇状细胞和Tm减少。消除Tm和随后再次感染Tm的小鼠仅在WT中导致2型免疫反应，但在WT和Raptor缺陷小鼠中都有Tm定植。当用IL-4刺激肠道类器官时，WT和Raptor缺陷类器官均可诱导簇状细胞和IL-25。总之，我们的研究表明，肠细胞特异性Raptor是启动2型免疫应答所必需的，而2型免疫应答似乎是通过调节mTORC1活性起作用的。
Intestinal tuft cells are one of 4 secretory cell linages in the small intestine and the source of IL-25, a critical initiator of the type 2 immune response to parasite infection. When Raptor, a critical scaffold protein for mammalian target of rapamycin complex 1 (mTORC1), was acutely deleted in intestinal epithelium via Tamoxifen injection in Tritrichomonas muris (Tm) infected mice, tuft cells, IL-25 in epithelium and IL-13 in the mesenchyme were significantly reduced, but Tm burden was not affected. When Tm infected mice were treated with rapamycin, DCLK1 and IL-25 expression in enterocytes and IL-13 expression in mesenchyme were diminished. After massive small bowel resection, tuft cells and Tm were diminished due to the diet used postoperatively. The elimination of Tm and subsequent re-infection of mice with Tm led to type 2 immune response only in WT, but Tm colonization in both WT and Raptor deficient mice. When intestinal organoids were stimulated with IL-4, tuft cells and IL-25 were induced in both WT and Raptor deficient organoids. In summary, our study reveals that enterocyte specific Raptor is required for initiating a type 2 immune response which appears to function through the regulation of mTORC1 activity.
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DOI：
10.1007/s11605-014-2631-0
发表时间：
2015-01
期刊：
Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract
影响因子：
--
作者：
Sommovilla J;Zhou Y;Sun RC;Choi PM;Diaz-Miron J;Shaikh N;Sodergren E;Warner BB;Weinstock GM;Tarr PI;Warner BW
通讯作者：
Warner BW
DOI：
10.1038/nri3901
发表时间：
2015-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Weichhart T;Hengstschläger M;Linke M
通讯作者：
Linke M
影响因子：
64.8
作者：
Gerbe F;Sidot E;Smyth DJ;Ohmoto M;Matsumoto I;Dardalhon V;Cesses P;Garnier L;Pouzolles M;Brulin B;Bruschi M;Harcus Y;Zimmermann VS;Taylor N;Maizels RM;Jay P
通讯作者：
Jay P
影响因子：
2.5
作者：
Bezencon, C.;Fuerholz, A.;Damak, S.
通讯作者：
Damak, S.
影响因子：
32.4
作者：
Urban, JF;Noben-Trauth, N;Finkelman, FD
通讯作者：
Finkelman, FD