Extrathymically Generated Regulatory T Cells Establish a Niche for Intestinal Border-Dwelling Bacteria and Affect Physiologic Metabolite Balance

被引：112

作者：

Campbell, Clarissa ^{[1
,2
,3
,4
]}

Dikiy, Stanislav ^{[1
,2
,3
,4
]}

Bhattarai, Shakti K. ^{[5
,6
]}

Chinen, Takatoshi ^{[1
,2
,3
]}

Matheis, Fanny ^{[7
]}

Calafiore, Marco ^{[8
]}

Hoyos, Beatrice ^{[1
,2
,3
]}

Hanash, Alan ^{[8
,9
]}

Mucida, Daniel ^{[7
]}

Bucci, Vanni ^{[5
]}

Rudensky, Alexander Y. ^{[1
,2
,3
,4
]}

机构：

[1] Howard Hughes Med Inst, New York, NY 10065 USA

[2] Sloan Kettering Inst, Immunol Program, New York, NY 10065 USA

[3] Mem Sloan Kettering Canc Ctr, Ludwig Ctr, New York, NY 10065 USA

[4] Weill Cornell Grad Sch Med Sci, Immunol & Microbial Pathogenesis Program, New York, NY 10021 USA

[5] Univ Massachusetts, Program Biotechnol & Biomed Engn, Dept Biol, Dartmouth, MA 02747 USA

[6] Univ Massachusetts, Dept Biol, Program Engn & Appl Sci, Dartmouth, MA 02747 USA

[7] Rockefeller Univ, Lab Mucosal Immunol, New York, NY 10065 USA

[8] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA

[9] Weill Cornell Med Coll, Dept Med, New York, NY 10021 USA

来源：

IMMUNITY | 2018年 / 48卷 / 06期

基金：

美国国家科学基金会;

关键词：

ALTERED SCHAEDLER FLORA; INNATE LYMPHOID-CELLS; GUT MICROBIOTA; COMMENSAL BACTERIA; ANTIGENS; GENE; DIFFERENTIATION; IMMUNITY;

D O I：

10.1016/j.immuni.2018.04.013

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

The mammalian gut microbiota provides essential metabolites to the host and promotes the differentiation and accumulation of extrathymically generated regulatory T (pTreg) cells. To explore the impact of these cells on intestinal microbial communities, we assessed the composition of the microbiota in pTreg cell-deficient and -sufficient mice. pTreg cell deficiency led to heightened type 2 immune responses triggered by microbial exposure, which disrupted the niche of border-dwelling bacteria early during colonization. Moreover, impaired pTreg cell generation led to pervasive changes in metabolite profiles, altered features of the intestinal epithelium, and reduced body weight in the presence of commensal microbes. Absence of a single species of bacteria depleted in pTreg cell-deficient animals, Mucispirillum schaedleri, partially accounted for the sequelae of pTreg cell deficiency. These observations suggest that pTreg cells modulate the metabolic function of the intestinal microbiota by restraining immune defense mechanisms that may disrupt a particular bacterial niche.

引用

页码：1245 / +

页数：22

共 66 条

[41]

Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 [J].