The mammalian Target of Rapamycin (mTOR) regulates T helper cell differentiation through the selective activation of mTORC1 and mTORC2 signaling

Abstract

mTOR has emerged as an important regulator of T helper cell differentiation. Here we demonstrate that T _H1 and T _H17 differentiation is selectively regulated by Rheb-dependent mTOR complex 1 (mTORC1) signaling. Rheb-deficient T cells fail to generate T _H1 and T _H17 responses in vitro and in vivo and cannot induce classical experimental autoimmune encephalomyelitis (EAE). However, they retain their ability to become T _H2 cells. Alternatively, when mTORC2 signaling is deleted in T cells, they fail to generate T _H2 cells in vitro and in vivo but preserve their ability to become T _H1 and T _H17 cells. Our data provide mechanisms by which the two distinct signaling pathways downstream of mTOR differentially regulate helper cell fate. These findings define a novel paradigm linking T cell differentiation with selective metabolic signaling pathways.