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.

RhoA GTPase plays a variety of functions in regulation of cytoskeletal proteins, cellular morphology, and migration along with various proliferation and transcriptional activity in cells. RhoA activity is regulated by guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs), and the guanine nucleotide dissociation factor (GDI). The RhoA-RhoGDI complex exists in the cytosol and the active GTP-bound form of RhoA is located to the membrane. GDI displacement factors (GDFs) including IκB kinase γ (IKKγ) dissociate the RhoA-GDI complex, allowing activation of RhoA through GEFs. In addition, modifications of Tyr42 phosphorylation and Cys16/20 oxidation in RhoA and Tyr156 phosphorylation and oxidation of RhoGDI promote the dissociation of the RhoA-RhoGDI complex. The expression of RhoA is regulated through transcriptional factors such as c-Myc, HIF-1α/2α, Stat 6, and NF-κB along with several reported microRNAs. As the role of RhoA in regulating actin-filament formation and myosin-actin interaction has been well described, in this review we focus on the transcriptional activity of RhoA and also the regulation of RhoA message itself. Of interest, in the cytosol, activated RhoA induces transcriptional changes through filamentous actin (F-actin)-dependent ("actin switch") or-independent means. RhoA regulates the activity of several transcription regulators such as serum response factor (SRF)/MAL, AP-1, NF-κB, YAP/TAZ, β-catenin, and hypoxia inducible factor (HIF)-1α. Interestingly, RhoA also itself is localized to the nucleus by an as-yet-undiscovered mechanism.