Poster Sessions

Imm-37

Arian Laurence

K. M. Elias, A. Laurence, T. S Davidson, G. Stephens, Y. Kanno, E. M. Shevach, J. J. O'Shea

Retinoic Acid Inhibits Th17 Polarization and Enhances FoxP3 Expression through a Stat-3/Stat-5 Independent Signaling Pathway

CD4+ helper T (Th) cells play a crucial role in the delicate balance between host defense and autoimmune disease. Two important populations of helper T cells are proinflammatory, interleukin-17-producing (Th17) cells and anti-inflammatory forkhead box P3 positive (FoxP3+) T regulatory (Treg) cells. Here we show that all-trans retinoic acid (ATRA) and other agonists of the retinoic acid receptor alpha (RARalpha) inhibit the formation of Th17 cells and promote FoxP3 expression. Conversely, inhibition of retinoic acid signaling constrains Transforming growth factor (TGF) beta-1 induction of FoxP3. The effect of ATRA is mediated independent of interleukin 2, signal transducer and activator of transcription (Stat)5 and Stat3, representing a novel mechanism for the induction of FoxP3 in CD4 T cells. As previous studies have shown that vitamin A derivatives are protective in animal models of autoimmune disease, the current data suggest a previously unrecognized role for RARalpha in the regulation of CD4+ T cell differentiation and provide a mechanism for the anti-inflammatory effects of retinoic acid.