Akt-1 and Akt-2 Differentially Regulate the Development of Experimental Autoimmune Encephalomyelitis by Controlling Proliferation of Thymus-Derived Regulatory T Cells

Song Ouyang, Qiuming Zeng, Na Tang, Hui Guo, Rong Tang, Weifan Yin, Aimin Wang, Hongyu Tang, Jiru Zhou, Hong Xie, Wallace Y. Langdon, Huan Yang, Jian Zhang

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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.

Original languageEnglish
Pages (from-to)1441-1452
Number of pages12
JournalJournal of Immunology
Issue number5
Publication statusPublished - 1 Mar 2019

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