ILC2s activated by IL-25 promote antigen-specific Th2 and Th9 functions that contribute to the control of Trichinella spiralis infection.
ILC2s activated by IL-25 promote antigen-specific Th2 and Th9 functions that contribute to the control of Trichinella spiralis infection.
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DOI：
10.1371/journal.pone.0184684
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Wang YH
中科院分区：
文献类型：
--
作者：
Angkasekwinai P;Sodthawon W;Jeerawattanawart S;Hansakon A;Pattanapanyasat K;Wang YH
IL-25是一种来源于上皮细胞的IL-17家族细胞因子，可调节Th2和Th9型免疫反应。我们以前曾报道，IL-25在促进对旋毛虫感染的有效保护性免疫中具有重要作用；然而，IL-25在感染过程中诱导2型免疫的细胞靶点尚未解决。在这里，我们研究了IL-25反应细胞及其在旋毛虫感染过程中介导2型免疫反应的作用。旋毛虫感染小鼠胃肠道中的ILC2和CD4+Th2细胞高水平表达IL-17RB，IL-17RB是IL-25受体的组成部分。在旋毛虫感染后，激活的ILC2s上调表面MHCII的表达，并通过MHCII依赖的相互作用增强效应T辅助细胞产生抗原特异性Th2和Th9细胞因子的能力。相反，在旋毛虫感染过程中，缺乏CD4+T辅助细胞会损害ILC2产生2型相关细胞因子的功能，以响应IL-25。此外，IL-17Rb缺乏的小鼠在旋毛虫感染过程中ILC2数量和抗原特异性Th2和Th9细胞因子的产生显著减少。Il17rb-/-小鼠未能安装有效的抗原特异性Th2和Th9功能，导致杯状细胞和肥大细胞反应减弱，导致肠道和肌肉中的蠕虫排出延迟。因此，我们的数据表明ILC2s和CD4+Th2细胞是旋毛虫感染后IL-25的主要细胞靶点，它们的协同作用可能在建立有效的抗原特异性Th2和Th9细胞因子应答抗旋毛虫感染中发挥关键作用。
IL-25, an IL-17 family cytokine, derived from epithelial cells was shown to regulate Th2- and Th9-type immune responses. We previously reported that IL-25 was important in promoting efficient protective immunity against T. spiralis infection; however, the cellular targets of IL-25 to elicit type-2 immunity during infection have not yet been addressed. Here, we investigated IL-25-responding cells and their involvement in mediating type-2 immune response during T. spiralis infection. ILC2 and CD4+ Th2 cells residing in the gastrointestinal tract of T. spiralis infected mice were found to express high levels of surface interleukin-17 receptor B (IL-17RB), a component of the IL-25 receptor. Following T. spiralis infection, activated ILC2s upregulated surface MHCII expression and enhanced capacity of effector T helper cell in producing antigen-specific Th2 and Th9 cytokines through MHCII-dependent interactions. Reciprocally, lack of CD4+ T helper cells impaired ILC2 function to produce type 2-associated cytokines in responding to IL-25 during T. spiralis infection. Furthermore, mice deficient in IL-17RB showed markedly reduced ILC2 numbers and antigen-specific Th2 and Th9 cytokine production during T. spiralis infection. The Il17rb-/- mice failed to mount effective antigen specific Th2 and Th9 functions resulting in diminished goblet cell and mast cell responses, leading to delayed worm expulsion in the intestines and muscles. Thus, our data indicated that ILC2s and CD4+ Th2 cells are the predominant cellular targets of IL-25 following T. spiralis infection and their collaborative interactions may play a key role in mounting effective antigen-specific Th2 and Th9 cytokine responses against T. spiralis infection.
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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：
30.5
作者：
通讯作者：
--
DOI：
10.1016/j.jaci.2015.09.019
发表时间：
2016-04
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Lee JB;Chen CY;Liu B;Mugge L;Angkasekwinai P;Facchinetti V;Dong C;Liu YJ;Rothenberg ME;Hogan SP;Finkelman FD;Wang YH
通讯作者：
Wang YH
影响因子：
4
作者：
Patel N;Kreider T;Urban JF Jr;Gause WC
通讯作者：
Gause WC
DOI：
10.4049/jimmunol.1400951
发表时间：
2015-04-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Liu B;Lee JB;Chen CY;Hershey GK;Wang YH
通讯作者：
Wang YH