Helminth-induced reprogramming of the stem cell compartment inhibits type 2 immunity.
Helminth-induced reprogramming of the stem cell compartment inhibits type 2 immunity.
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DOI：
10.1084/jem.20212311
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发表时间：
2022-09-05
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--
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Karo-Atar等人证明了肠道蠕虫对肠道干细胞区室的直接调节，导致胎儿样干细胞的扩增和分泌细胞的抑制。他们建立了蠕虫寄生虫如何选择组织发育程序来对抗2型免疫介导的驱逐。肠道蠕虫与肠上皮形成密切的物理连接，但它们直接改变上皮干细胞命运的能力尚未得到解决。在这里，我们证明了感染寄生虫Heligmosomoides polygyrus bakeri（Hpb）的小鼠将肠上皮重新编程为胎儿样状态，其标志是出现了表达白细胞介素的复兴干细胞（revSC）。使用寄生虫衍生的排泄分泌产物的基于类器官的研究揭示，Hp介导的revSC生成独立于宿主衍生的免疫信号发生，并抑制促进其排出的分泌上皮谱系的2型丝氨酸驱动的分化。反过来，2型细胞因子信号限制了revSC分化，因此限制了Hpb适应性，这表明蠕虫与宿主竞争肠道干细胞区室的控制，以促进其生命周期的延续。
Karo-Atar et al. demonstrate direct regulation of the intestinal stem cell compartment by an enteric helminth, resulting in expansion of fetal-like stem cells and inhibition of secretory cells. They establish how a helminth parasite co-opts a tissue development program to counter type 2 immune-mediated expulsion. Enteric helminths form intimate physical connections with the intestinal epithelium, yet their ability to directly alter epithelial stem cell fate has not been resolved. Here we demonstrate that infection of mice with the parasite Heligmosomoides polygyrus bakeri (Hpb) reprograms the intestinal epithelium into a fetal-like state marked by the emergence of Clusterin-expressing revival stem cells (revSCs). Organoid-based studies using parasite-derived excretory-secretory products reveal that Hpb-mediated revSC generation occurs independently of host-derived immune signals and inhibits type 2 cytokine–driven differentiation of secretory epithelial lineages that promote their expulsion. Reciprocally, type 2 cytokine signals limit revSC differentiation and, consequently, Hpb fitness, indicating that helminths compete with their host for control of the intestinal stem cell compartment to promote continuation of their life cycle.
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影响因子：
1.5
作者：
Hewitson, James P.;Grainger, John R.;Maizels, Rick M.
通讯作者：
Maizels, Rick M.
影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
14.9
作者：
Babicki S;Arndt D;Marcu A;Liang Y;Grant JR;Maciejewski A;Wishart DS
通讯作者：
Wishart DS
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
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