Control of T cell metabolism and regulatory T cell generation by a DRAK2/p70S6K1 signaling axis (113.19)
| Autor: | Jeniffer Hernandez, Ryan Michalek, Brian Weist, Ryan Newton, Jose Limon, Mayra Carrillo, Elyse Paterson, Long Nguyen, David Fruman, Jeffrey Rathmell, Craig Walsh |
|---|---|
| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 186:113.19-113.19 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | 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 highly expressed in lymphocytes, may offer an alternative and selective approach vs. rapamycin in the suppression of autoimmunity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|