Faecalibaculum rodentium remodels retinoic acid signaling to govern eosinophil-dependent intestinal epithelial homeostasis.
Faecalibaculum rodentium remodels retinoic acid signaling to govern eosinophil-dependent intestinal epithelial homeostasis.
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DOI：
10.1016/j.chom.2022.07.015
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发表时间：
2022-09-14
影响因子：
30.3
通讯作者：
Garrett, Wendy S.
中科院分区：
文献类型：
--
作者：
Cao, Y. Grace;Bae, Sena;Villarreal, Jannely;Moy, Madelyn;Chun, Eunyoung;Michaud, Monia;Lang, Jessica K.;Glickman, Jonathan N.;Lobel, Lior;Garrett, Wendy S.
肠上皮在感知和整合饮食和微生物信号方面发挥着关键作用。微生物群和肠上皮细胞（IEC）如何相互作用调节近端小肠，特别是十二指肠的宿主生理，目前尚不清楚。通过对无菌（GF）和不同传统微生物群组成下的十二指肠IECs进行单细胞RNA测序，我们发现特定的微生物群成员通过增加上皮周转率、隐窝增殖和主要组织相容性复合体II类（MHCII）的表达来改变上皮稳态。微生物组分析鉴定出粪足菌是参与这一调控的关键物种。F. rodentium降低肠细胞中产生维甲酸-25的酶Adh1、Aldh1a1和Rdh7的表达，减少维持某些肠道嗜酸性粒细胞群体所需的维甲酸信号传导。嗜酸性粒细胞抑制上皮内淋巴细胞介导的调节上皮细胞功能的干扰素γ的产生。因此，我们确定了维甲酸-嗜酸性粒细胞-干扰素-γ依赖回路，微生物群通过该回路调节十二指肠上皮稳态。肠上皮是微生物群和免疫系统之间交流的中心节点。Cao等人的研究表明，Faecalibaculum rodentium可以通过抑制维甲酸的产生来促进上皮细胞的增殖和更新，维甲酸支持肠道嗜酸性粒细胞的存活，进而抑制促增殖的IFN-γ的产生。
The intestinal epithelium plays critical roles in sensing and integrating dietary and microbial signals. How microbiota and intestinal epithelial cell (IEC) interactions regulate host physiology in the proximal small intestine, particularly the duodenum, is unclear. Using single-cell RNA sequencing of duodenal IECs under germ-free (GF) and different conventional microbiota compositions, we show that specific microbiota members alter epithelial homeostasis by increasing epithelial turnover rate, crypt proliferation, and major histocompatibility complex class II (MHCII) expression. Microbiome profiling identified Faecalibaculum rodentium as a key species involved in this regulation. F. rodentium decreases enterocyte expression of retinoic acid-25 producing enzymes Adh1, Aldh1a1, and Rdh7, reducing retinoic acid signaling required to maintain certain intestinal eosinophil populations. Eosinophils suppress intraepithelial lymphocyte-mediated production of interferon-γ that regulates epithelial cell function. Thus, we identify a retinoic acid-eosinophil-interferon-γ-dependent circuit by which the microbiota modulates duodenal epithelial homeostasis. The intestinal epithelium is a central node for communication between the microbiota and immune system. Cao et al. show that Faecalibaculum rodentium can promote epithelial proliferation and turnover by dampening retinoic acid production that supports survival of intestinal eosinophils, which in turn suppress pro-proliferative IFN-γ production.
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影响因子：
32.4
作者：
Hall JA;Cannons JL;Grainger JR;Dos Santos LM;Hand TW;Naik S;Wohlfert EA;Chou DB;Oldenhove G;Robinson M;Grigg ME;Kastenmayer R;Schwartzberg PL;Belkaid Y
通讯作者：
Belkaid Y
影响因子：
64.5
作者：
Chen B;Scurrah CR;McKinley ET;Simmons AJ;Ramirez-Solano MA;Zhu X;Markham NO;Heiser CN;Vega PN;Rolong A;Kim H;Sheng Q;Drewes JL;Zhou Y;Southard-Smith AN;Xu Y;Ro J;Jones AL;Revetta F;Berry LD;Niitsu H;Islam M;Pelka K;Hofree M;Chen JH;Sarkizova S;Ng K;Giannakis M;Boland GM;Aguirre AJ;Anderson AC;Rozenblatt-Rosen O;Regev A;Hacohen N;Kawasaki K;Sato T;Goettel JA;Grady WM;Zheng W;Washington MK;Cai Q;Sears CL;Goldenring JR;Franklin JL;Su T;Huh WJ;Vandekar S;Roland JT;Liu Q;Coffey RJ;Shrubsole MJ;Lau KS
通讯作者：
Lau KS
影响因子：
6.4
作者：
Comeau AM;Douglas GM;Langille MG
通讯作者：
Langille MG
DOI：
10.1073/pnas.1304046110
发表时间：
2013-06-11
影响因子：
11.1
作者：
Goh, Y. P. Sharon;Henderson, Neil C.;Chawla, Ajay
通讯作者：
Chawla, Ajay
影响因子：
--
作者：
Germain, Pierre;Gaudon, Claudine;Gronemeyer, Hinrich
通讯作者：
Gronemeyer, Hinrich