Control of T cell metabolism and regulatory T cell generation by a DRAK2/p70S6K1 signaling axis (113.19)

TL;DRAbstract

Abstract The delicate balance between effector T cells (Teff cells) and regulatory T cells (Treg cells) is crucial for preventing autoimmunity while maintaining efficient immune function. Mice deficient in the serine/threonine kinase, Dap Related Apoptosis inducing Kinase 2 (DRAK2), are resistant to T cell-mediated organ-specific autoimmune diseases yet retain antiviral immunity. Here we show that DRAK2 dictates the fate of a naïve T cells by regulating their metabolism. This is achieved through amplifying the activity of p70S6K1 in a parallel manner to mTORC1, which leads to an increase in glycolytic metabolism, a process required for Teff cell survival. In addition, we find that the inhibition of the DRAK2/p70S6K1 axis promotes the generation of Treg cells similar to mTORC1 inhibition with rapamycin. By regulating T cell metabolism and Treg cell generation, the DRAK2/p70S6K1 signaling axis orchestrates the balance between Teff cells and Treg cells. Blockade of DRAK2, which is most h

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