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

α4 and β7 integrins such as α4β1, α4β7 and αEβ7 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-α4 subunit by both CD4(+) and CD8(+) T cells requires the retinoic acid signal. In contrast, transcription of Itg-αE genes is induced by the TGFβ1 signal. Expression of Itg-β7 is constitutive but can be further increased by TGFβ1. Consistently, expression of α4-containing integrins is severely suppressed in vitamin A deficiency with a compensatory increase of αEβ7, whereas expression of Itg-αE and Itg-β7 is decreased in TGFβ-signal deficiency with a compensatory increase in α4β1. The retinoic acid-mediated regulation of α4 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.