| First Author | Ouyang S | Year | 2019 |
| Journal | J Immunol | Volume | 202 |
| Issue | 5 | Pages | 1441-1452 |
| PubMed ID | 30692211 | Mgi Jnum | J:272998 |
| Mgi Id | MGI:6280852 | Doi | 10.4049/jimmunol.1701204 |
| Citation | Ouyang S, et al. (2019) Akt-1 and Akt-2 Differentially Regulate the Development of Experimental Autoimmune Encephalomyelitis by Controlling Proliferation of Thymus-Derived Regulatory T Cells. J Immunol 202(5):1441-1452 |
| abstractText | Akt isoforms play key roles in multiple cellular processes; however, the roles of Akt-1 and Akt-2 isoforms in the development of T cell-mediated autoimmunity are poorly defined. In this study, we showed that Akt1(-/-) mice develop ameliorated experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, whereas Akt2(-/-) mice develop exacerbated EAE, compared with wild-type mice. At the cellular level, Akt-1 appears to inhibit proliferation of thymus-derived regulatory T cells (tTregs), which facilitates Ag-specific Th1/Th17 responses. In a sharp contrast to Akt-1, Akt-2 potentiates tTreg proliferation in vitro and in vivo and suppresses Ag-specific Th1/Th17 responses. Furthermore, treating mice with established EAE with a specific Akt-1 inhibitor suppressed disease progression. Our data demonstrate that Akt-1 and Akt-2 differentially regulate the susceptibility of mice to EAE by controlling tTreg proliferation. Our data also indicate that targeting Akt-1 is a potential therapeutic approach for multiple sclerosis in humans. |
