Epithelial cell-specific Act1 adaptor mediates interleukin-25-dependent helminth expulsion through expansion of Lin(-)c-Kit(+) innate cell population.
Epithelial cell-specific Act1 adaptor mediates interleukin-25-dependent helminth expulsion through expansion of Lin(-)c-Kit(+) innate cell population.
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DOI：
10.1016/j.immuni.2012.03.021
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发表时间：
2012-05-25
期刊：
影响因子：
32.4
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Kang Z;Swaidani S;Yin W;Wang C;Barlow JL;Gulen MF;Bulek K;Do JS;Aronica M;McKenzie AN;Min B;Li X
白介素25(IL-25或IL-17E)是结构上相关的IL-17家族成员，是辅助性T细胞2型(T2型)应答的重要介体。我们研究了IL-25诱导的Act1介导的信号在针对蠕虫感染的保护性免疫中的细胞类型特异性作用。靶向ACT1缺失的上皮细胞可显著延迟驱虫，并抑制肠系膜淋巴结、肺和肝脏中LIN−c-Kit+天然细胞群的扩张。Th2细胞诱导的细胞因子(IL-25和IL-33)在感染和注射上皮细胞特异性Act1缺陷小鼠的肠上皮细胞中的表达减少。过继转移LIN−c-Kit+细胞或联合注射IL-25和IL-33可恢复这些小鼠的2型反应。综上所述，这些结果提示，上皮特异性ACT1通过IL-25的正反馈环，介导LIN−c-Kit+天然细胞群的扩张，启动针对蠕虫感染的2型免疫。
Interleukin-25 (IL-25 or IL-17E), a member of the structurally related IL-17 family, functions as an important mediator of T helper 2 cell-type (type 2) responses. We examined the cell-type specific role of IL-25-induced Act1-mediated signaling in protective immunity against helminth infection. Targeted Act1 deficiency in epithelial cells resulted in a marked delay in worm expulsion and abolished the expansion of the Lin−c-kit+ innate cell population in the mesenteric lymph node, lung and liver. Th2 cell-inducing cytokines (IL-25 and IL-33) expression were reduced in the intestinal epithelial cells from the infected and IL-25-injected epithelial-specific Act1-deficient mice. Adoptive transfer of Lin−c-kit+ cells or combined injection of IL-25 and IL-33 restored the type 2 responses in these mice. Taken together, these results suggest that epithelial-specific Act1 mediates the expansion of the Lin−c-kit+ innate cell population through the positive feedback loop of IL-25, initiating the type 2 immunity against helminth infection.
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影响因子：
9
作者：
Ho, Allen W.;Gaffen, Sarah L.
通讯作者：
Gaffen, Sarah L.
影响因子：
4.4
作者：
Claudio, Estefania;Sonder, Soren Ulrik;Saret, Sun;Carvalho, Gabrielle;Ramalingam, Thirumalai R.;Wynn, Thomas A.;Chariot, Alain;Garcia-Perganeda, Antonio;Leonardi, Antonio;Paun, Andrea;Chen, Amy;Ren, Nina Y.;Wang, Hongshan;Siebenlist, Ulrich
通讯作者：
Siebenlist, Ulrich
影响因子：
4.8
作者：
Chang SH;Dong C
通讯作者：
Dong C
影响因子：
32.4
作者：
Kang Z;Altuntas CZ;Gulen MF;Liu C;Giltiay N;Qin H;Liu L;Qian W;Ransohoff RM;Bergmann C;Stohlman S;Tuohy VK;Li X
通讯作者：
Li X
DOI：
10.1084/jem.20091268
发表时间：
2009-12-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Herbert DR;Yang JQ;Hogan SP;Groschwitz K;Khodoun M;Munitz A;Orekov T;Perkins C;Wang Q;Brombacher F;Urban JF Jr;Rothenberg ME;Finkelman FD
通讯作者：
Finkelman FD