Glycoantigens Induce Human Peripheral Tr1 Cell Differentiation with Gut-homing Specialization
Glycoantigens Induce Human Peripheral Tr1 Cell Differentiation with Gut-homing Specialization
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DOI：
10.1074/jbc.m110.206011
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发表时间：
2011-03-18
影响因子：
4.8
通讯作者：
Cobb, Brian A.
中科院分区：
文献类型：
--
作者：
Kreisman, Lori S. C.;Cobb, Brian A.
The carbohydrate antigen (glycoantigen) PSA from an intestinal commensal bacteria is able to down-regulate inflammatory bowel disease in model mice, suggesting that stimulation with PSA results in regulatory T cell (Treg) generation. However, mechanisms of how peripheral human T cells respond and home in response to commensal antigens are still not understood. Here, we demonstrate that a single exposure to PSA induces differentiation of human peripheral CD4(+) T cells into type-Tr1 Tregs. This is in contrast to mouse models where PSA induced the production of Foxp3(+) iTregs. The human PSA-induced Tr1 cells are profoundly anergic and exhibit nonspecific bystander suppression mediated by IL-10 secretion. Most surprisingly, glycoantigen exposure provoked expression of gut homing receptors on their surface. These findings reveal a mechanism for immune homeostasis in the gut whereby exposure to commensal glycoantigens provides the requisite information to responding T cells for proper tissue localization (gut) and function (anti-inflammatory/regulatory).
