All-trans Retinoic Acid Mediates Enhanced T Reg Cell Growth, Differentiation, and Gut Homing in the Face of High Levels of Co-stimulation

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2007 Jul 11

PMID 17620363

Citations 433

Authors

Micah J Benson

Karina Pino-Lagos

Mario Rosemblatt

Randolph J Noelle

Affiliations

Soon will be listed here.

Abstract

We demonstrate that all-trans retinoic acid (RA) induces FoxP3(+) adaptive T regulatory cells (A-Tregs) to acquire a gut-homing phenotype (alpha 4 beta 7(+) CC chemokine receptor 9(+)) and the capacity to home to the lamina propria of the small intestine. Under conditions that favor the differentiation of A-Tregs (transforming growth factor-beta1 and interleukin 2) in vitro, the inclusion of RA induces nearly all activated CD4(+) T cells to express FoxP3 and greatly increases the accumulation of these cells. In the absence of RA, A-Treg differentiation is abruptly impaired by proficient antigen presenting cells or through direct co-stimulation. In the presence of RA, A-Treg generation occurs even in the presence of high levels of co-stimulation, with RA attenuating co-stimulation from interfering from FoxP3 induction. The recognition that RA induces gut imprinting, together with our finding that it enhances A-Treg conversion, differentiation, and expansion, indicates that RA production in vivo may drive both the imprinting and A-Treg development in the face of overt inflammation.

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