The Journal of Experimental Medicine
Geisel School of Medicine
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.
Benson MJ, Pino-Lagos K, Rosemblatt M, Noelle RJ. All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation. J Exp Med. 2007 Aug 6;204(8):1765-74. doi: 10.1084/jem.20070719. Epub 2007 Jul 9. PMID: 17620363; PMCID: PMC2118687.
Dartmouth Digital Commons Citation
Benson, Micah J.; Pino-Lagos, Karina; Rosemblatt, Mario; and Noelle, Randolph J., "All-trans Retinoic Acid Mediates Enhanced T Reg Cell Growth, Differentiation, and Gut Homing in the Face of High Levels of Co-Stimulation" (2007). Dartmouth Scholarship. 1147.