A conserved Bacteroidetes antigen induces anti-inflammatory intestinal T lymphocytes

被引：69

作者：

Bousbaine, Djenet ^{[1
,2
,3
,15
]}

Fisch, Laura, I ^{[2
]}

London, Mariya ^{[4
]}

Bhagchandani, Preksha ^{[2
,3
]}

de Castro, Tiago B. Rezende ^{[4
,5
]}

Mimee, Mark ^{[3
,6
,7
]}

Olesen, Scott ^{[3
,8
]}

Reis, Bernardo S. ^{[4
]}

VanInsberghe, David ^{[1
,9
]}

Bortolatto, Juliana ^{[5
]}

Poyet, Mathilde ^{[3
,8
]}

Cheloha, Ross W. ^{[2
]}

Sidney, John ^{[10
]}

Ling, Jingjing ^{[2
]}

Gupta, Aaron ^{[4
]}

Lu, Timothy K. ^{[3
,6
,7
]}

Sette, Alessandro ^{[10
,11
]}

Alm, Eric J. ^{[3
,8
]}

Moon, James J. ^{[12
,13
]}

Victora, Gabriel D. ^{[5
]}

Mucida, Daniel ^{[4
,14
]}

Ploegh, Hidde L. ^{[2
,3
]}

Bilate, Angelina M. ^{[3
,4
]}

机构：

[1] Massachussetts Inst Technol MIT, Microbiol Grad Program, Cambridge, MA USA

[2] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA

[3] MIT, Ctr Microbiome Informat & Therapeut, Cambridge, MA 02139 USA

[4] Rockefeller Univ, Lab Mucosal Immunol, New York, NY 10021 USA

[5] Rockefeller Univ, Lab Lymphocyte Dynam, New York, NY USA

[6] MIT, Synthet Biol Ctr, Cambridge, MA USA

[7] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA

[8] MIT, Dept Biol Engn, Cambridge, MA USA

[9] MIT, Dept Civil & Environm Engn, Cambridge, MA USA

[10] La Jolla Inst Immunol, Div Vaccine Discovery, La Jolla, CA USA

[11] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA

[12] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA USA

[13] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA USA

[14] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA

[15] Stanford Univ, Dept Bioengn, Dept Microbiol & Immunol, ChEM H Inst, Stanford, CA 94305 USA

来源：

SCIENCE | 2022年 / 377卷 / 6606期

基金：

瑞士国家科学基金会;

关键词：

CELLS; SUBSETS; MICE;

D O I：

10.1126/science.abg5645

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The microbiome contributes to the development and maturation of the immune system. In response to commensal bacteria, intestinal CD4(+) T lymphocytes differentiate into functional subtypes with regulatory or effector functions. The development of small intestine intraepithelial lymphocytes that coexpress CD4 and CD8(alpha alpha) homodimers (CD4IELs) depends on the microbiota. However, the identity of the microbial antigens recognized by CD4(+) T cells that can differentiate into CD4IELs remains unknown. We identified beta-hexosaminidase, a conserved enzyme across commensals of the Bacteroidetes phylum, as a driver of CD4IEL differentiation. In a mouse model of colitis, b-hexosaminidase-specific lymphocytes protected against intestinal inflammation. Thus, T cells of a single specificity can recognize a variety of abundant commensals and elicit a regulatory immune response at the intestinal mucosa.

引用

页码：660 / +

页数：7

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