Complementary roles of retinoic acid and TGF-β1 in coordinated expression of mucosal integrins by T cells.

α(4) and β(7) integrins, such as α(4)β(1), α(4)β(7), and α(E)β(7), are major integrins required for migration of leukocytes into mucosal tissues. The mechanisms responsible for coordinated expression of these three integrins have been poorly elucidated to date. We report that expression of the Itg-α(4) subunit by both CD4(+) and CD8(+) T cells requires the retinoic acid signal. In contrast, transcription of Itg-α(E) genes is induced by the transforming growth factor-β1 (TGFβ1) signal. Expression of Itg-β(7) is constitutive but can be further increased by TGFβ1. Consistently, expression of α(4)-containing integrins is severely suppressed in vitamin A deficiency with a compensatory increase of α(E)β(7), whereas expression of Itg-α(E) and Itg-β(7) is decreased in TGFβ-signal deficiency with a compensatory increase in α(4)β(1). The retinoic acid-mediated regulation of α(4) integrins is required for specific migration of T cells in vitro and in vivo. These results provide central regulatory mechanisms for coordinated expression of the major mucosal integrins.