Specific AKT3 activator and uses thereof
A technology of solvates and enantiomers, applied in the field of regulating regulatory T cells, can solve problems such as the unclear role of Akt isoforms
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Embodiment 1
[0255] Example 1: mJJ64A significantly increases the expression of FoxP3 on iTreg.
[0256] result
[0257] The data showed that mJJ64A significantly increased the expression of FoxP3 on iTregs and slightly increased the proliferation of iTregs ( Figure 2A to Figure 2H ).
Embodiment 2
[0258] Example 2: Addition of mJJ64A during iTreg induction increases FoxP3 expression.
[0259] result
[0260] The data showed that mJJ64A increased FoxP3 expression when added during iTreg induction ( Figure 3A and Figure 3B ).
Embodiment 3
[0261] Example 3: Akt3 specifically regulates two types of Tregs, nTreg and iTreg.
[0262] result
[0263] The data showed that Akt3 is a key regulator of nTreg ( Figure 4A to Figure 4F ). The suppressive activity of Tregs from Akt3 KO mice was due to reduced levels of suppressive cytokines IL-10 and TGFβ ( Figure 4E and Figure 4F ). The data also showed that the suppressive activity of Treg was impaired in vivo in the absence of Akt3 but in the presence of other isoforms ( Figure 5A to Figure 5B ). Tregs from Akt3 KO mice showed impaired inhibitory activity in the RAG colitis model ( Figure 5A ). Furthermore, adoptive transfer of Tregs from Akt3 KO mice to Treg-depleted tumor-bearing mice showed impaired antitumor immunosuppression ( Figure 5B ).
[0264] The data also showed that Akt3 is a key regulator of iTreg ( Figure 6A to Figure 6E ). Akt3 RNA, protein and Akt3 phosphorylation were upregulated in iTreg ( Figure 6A to Figure 6C ). In Akt3 KO mice,...
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