T Helper Cell Cytokines Modulate Intestinal Stem Cell Renewal and Differentiation.
T Helper Cell Cytokines Modulate Intestinal Stem Cell Renewal and Differentiation.
复制标题
DOI：
10.1016/j.cell.2018.10.008
复制
发表时间：
2018-11-15
期刊：
影响因子：
64.5
通讯作者：
Xavier RJ
中科院分区：
文献类型：
--
作者：
Biton M;Haber AL;Rogel N;Burgin G;Beyaz S;Schnell A;Ashenberg O;Su CW;Smillie C;Shekhar K;Chen Z;Wu C;Ordovas-Montanes J;Alvarez D;Herbst RH;Zhang M;Tirosh I;Dionne D;Nguyen LT;Xifaras ME;Shalek AK;von Andrian UH;Graham DB;Rozenblatt-Rosen O;Shi HN;Kuchroo V;Yilmaz OH;Regev A;Xavier RJ
在小肠中，辅助细胞类型的生态位支持肠道干细胞（ISC）生成成熟的上皮细胞类型。然而，目前尚不清楚生态位中的免疫细胞是否以及如何影响 ISC 命运或自我更新与分化之间的平衡。在这里，我们使用单细胞 RNA-seq 来鉴定 Lgr5+ ISC 的两个子集中的 MHC II 类 (MHCII) 机制富集。我们发现 MHCII+ Lgr5+ ISC 是与 CD4+ T 辅助 (Th) 细胞共培养的非常规抗原呈递细胞。用关键 Th 细胞因子刺激肠道类器官，以相反的方式影响 Lgr5+ ISC 的更新和分化：促炎信号促进分化，而调节细胞和细胞因子则减少分化。 Th 细胞的体内遗传扰动或 Lgr5+ ISC 上的 MHCII 表达会影响感染期间的上皮细胞分化和 IEC 命运。 Th 细胞和 Lgr5+ ISC 之间的相互作用从而协调组织范围内对外部信号的反应。肠道干细胞充当非常规抗原呈递细胞，这些与 T 辅助细胞的相互作用可调节 ISC 更新和分化，从而塑造肠道
In the small intestine, a niche of accessory cell types supports the generation of mature epithelial cell types from intestinal stem cells (ISCs). It is unclear however if and how immune cells in the niche affect ISC fate or the balance between self-renewal and differentiation. Here, we use single-cell RNA-seq to identify MHC class II (MHCII) machinery enrichment in two subsets of Lgr5+ ISCs. We show that MHCII+ Lgr5+ ISCs are non-conventional antigen presenting cells in co-cultures with CD4+ T helper (Th) cells. Stimulation of intestinal organoids with key Th cytokines affects Lgr5+ ISC renewal and differentiation in opposing ways: pro-inflammatory signals promote differentiation, while regulatory cells and cytokines reduce it. In vivo genetic perturbation of Th cells or MHCII expression on Lgr5+ ISCs impacts epithelial cell differentiation and IEC fate during infection. These interactions between Th cells and Lgr5+ ISCs thus orchestrate tissue-wide responses to external signals. Intestinal stem cells act as non-conventional antigen presenting cells and these interactions with T helper cells modulate ISC renewal and differentiation to shape the intestine
登录
查看更多内容
影响因子：
64.8
作者：
Esplugues, Enric;Huber, Samuel;Gagliani, Nicola;Hauser, Anja E.;Town, Terrence;Wan, Yisong Y.;O'Connor, William, Jr.;Rongvaux, Anthony;Van Rooijen, Nico;Haberman, Ann M.;Iwakura, Yoichiro;Kuchroo, Vijay K.;Kolls, Jay K.;Bluestone, Jeffrey A.;Herold, Kevan C.;Flavell, Richard A.
通讯作者：
Flavell, Richard A.
影响因子：
32.4
作者：
Agudo J;Park ES;Rose SA;Alibo E;Sweeney R;Dhainaut M;Kobayashi KS;Sachidanandam R;Baccarini A;Merad M;Brown BD
通讯作者：
Brown BD
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：
64.8
作者：
Buczacki, Simon J. A.;Zecchini, Heather Ireland;Winton, Douglas J.
通讯作者：
Winton, Douglas J.
影响因子：
3.7
作者：
Howie D;Garcia Rueda H;Brown MH;Waldmann H
通讯作者：
Waldmann H