mTOR regulates CD4 and CD8 effector T cell differentiation via serum- and glucocorticoid-regulated kinase 1 (P1161)

• Published in: The Journal of immunology (1950) 2013-05, Vol.190 (1_Supplement), p.50-50.23
• Main Authors: Heikamp, Emily, Patel, Chirag, Collins, Sam, Waickman, Adam, Scharma, Archna, Naray-Fejes-Toth, Aniko, Fejes-Toth, Geza, Sen, Jyoti, Horton, Maureen, Powell, Jonathan
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.190.Supp.50.23

The mammalian target of rapamycin (mTOR) signaling pathway is a master regulator of T cell differentiation. mTOR integrates various signals in the immune microenvironment, including costimulatory ligands, cytokines, and the availability of nutrients to determine the outcome of T cell differentiation. Recently, we identified the serum- and glucocorticoid-regulated kinase 1 (SGK1) as a downstream target of mTORC2 that is a critical regulator of CD4 effector differentiation into Th1 and Th2 subsets. Specifically, SGK1 promotes Th2 differentiation by negatively regulating the NEDD4-2 E3 ligase mediated destruction of JunB. Simultaneously, SGK1 represses the production of IFN-γ by controlling the expression of the long isoform of TCF-1. Consistent with these functions, mice lacking SGK1 specifically in T cells fail to generate a Th2 response and are resistant to experimentally induced asthma. Likewise, such mice generate robust levels of IFN-γ in response to vaccines and more readily reject tumors. In addition, loss of SGK1 in CD8 T cells promotes memory differentiation by regulating the expression of CD127, CD62L, and eomesodermin. In summary, our findings reveal a novel role for SGK1 as an essential component of the mTOR pathway that guides differentiation of both CD4 and CD8 T cells. Targeting SGK1, therefore, may be a useful strategy for fine-tuning immune responses by manipulating T cell differentiation.