Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites.
Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites.
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DOI：
10.1038/nature16527
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发表时间：
2016-01-14
期刊：
影响因子：
64.8
通讯作者：
Jay P
中科院分区：
文献类型：
--
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
蠕虫寄生虫感染是一个主要的全球健康和社会负担。2型细胞介导的免疫系统对蠕虫如巴西尼圆线虫的宿主防御诱导2型细胞因子，包括白细胞介素（IL）IL-4和IL-13，诱导杯状细胞增生并产生粘液，最终导致蠕虫排出。然而，启动2型反应的机制仍然不完全清楚。在这里，我们表明，簇状细胞，一种罕见的上皮细胞类型的稳态肠上皮，负责启动2型反应寄生虫的精氨酸介导的细胞中继。簇状细胞具有Th 2相关基因表达特征，我们证明，由于上皮隐窝祖细胞的直接分化，它们在感染蠕虫寄生虫后经历快速和广泛的IL-4 R α依赖性扩增。我们发现Pou 2f 3基因对簇状细胞特异性是必不可少的。Pou 2f 3 −/−小鼠缺乏肠簇状细胞，对蠕虫感染有缺陷的粘膜2型反应;杯状细胞增生被废除，蠕虫驱逐受到影响。值得注意的是，IL-4 R α信号传导足以诱导簇状细胞谱系的扩增，并且该信号传导级联的异位刺激消除了在肠上皮细胞重塑中对簇状细胞的需要。此外，簇细胞分泌IL-25，从而调节2型免疫应答。我们的数据揭示了肠上皮簇细胞的一种新功能，并证明了启动粘膜2型免疫蠕虫感染所需的细胞中继。
Helminth parasitic infections are a major global health and social burden. The host defence against helminths such asNippostrongylus brasiliensisis orchestrated by type 2 cell-mediated immunity. Induction of type 2 cytokines, including interleukins (IL) IL-4 and IL-13, induce goblet cell hyperplasia with mucus production, ultimately resulting in worm expulsion,. However, the mechanisms underlying the initiation of type 2 responses remain incompletely understood. Here we show that tuft cells, a rare epithelial cell type in the steady-state intestinal epithelium, are responsible for initiating type 2 responses to parasites by a cytokine-mediated cellular relay. Tuft cells have a Th2-related gene expression signature and we demonstrate that they undergo a rapid and extensive IL-4Rα-dependent amplification following infection with helminth parasites, owing to direct differentiation of epithelial crypt progenitor cells. We find that thePou2f3gene is essential for tuft cell specification.Pou2f3−/−mice lack intestinal tuft cells and have defective mucosal type 2 responses to helminth infection; goblet cell hyperplasia is abrogated and worm expulsion is compromised. Notably, IL-4Rα signalling is sufficient to induce expansion of the tuft cell lineage, and ectopic stimulation of this signalling cascade obviates the need for tuft cells in the epithelial cell remodelling of the intestine. Moreover, tuft cells secrete IL-25, thereby regulating type 2 immune responses. Our data reveal a novel function of intestinal epithelial tuft cells and demonstrate a cellular relay required for initiating mucosal type 2 immunity to helminth infection.
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影响因子：
21.3
作者：
通讯作者：
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DOI：
10.1083/jcb.200311021
发表时间：
2004-07-05
期刊：
The Journal of cell biology
影响因子：
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作者：
Blache P;van de Wetering M;Duluc I;Domon C;Berta P;Freund JN;Clevers H;Jay P
通讯作者：
Jay P
DOI：
10.4049/jimmunol.1000450
发表时间：
2010-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Zhao A;Urban JF Jr;Sun R;Stiltz J;Morimoto M;Notari L;Madden KB;Yang Z;Grinchuk V;Ramalingam TR;Wynn TA;Shea-Donohue T
通讯作者：
Shea-Donohue T
DOI：
10.1084/jem.20091268
发表时间：
2009-12-21
期刊：
The Journal of experimental medicine
影响因子：
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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
DOI：
10.1073/pnas.85.12.4460
发表时间：
1988-06-01
影响因子：
11.1
作者：
WATANABE, N;KATAKURA, K;OVARY, Z
通讯作者：
OVARY, Z