The Hippo pathway is involved in T cell development. In the thymus, MST1/2 are more expressed in single-positive (SP) thymocytes than in double-positive (DP) thymocytes in the thymus. NDR1/2 regulate the egress of naive T cells from the thymus and migration to the periphery. MST1/2 regulates T cell migration by activating MOB1A/B, which is required for the activation of the guanyl nucleotide exchanger Dock8, and by promoting LFA-1 clustering through direct interaction with the small GTPase Rap1-binding effector protein RAPL. MST1/2 also enhances regulatory T (Treg) cell differentiation by stabilizing FOXO1/3 or attenuating TCR-stimulated AKT activity. TAZ suppresses Treg differentiation by inhibiting FOXP3 via the TAZ-RORγt complex. TAZ stimulates Th17 cell differentiation through a complex with RORγt. MST1/2 in dendritic cells affect Th17 cells differentiations by inhibiting p38MAPK-MK2/MSK1-CREB signaling, which is implicated in IL-6 production.
