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PRMT5 in T helper lymphocytes is essential for cholesterol biosynthesis-mediated Th17 responses and autoimmunity

Webb, L. M.; Sengupta, S.; Edell, C.; Amici, S. A.; Narvaez-Miranda, J.; Kennemer, A.; Guerau-de-Arellano, M.

2019-10-03 immunology
10.1101/792788 bioRxiv
Show abstract

Protein Arginine Methyltransferase (PRMT) 5 catalyzes symmetric dimethylation of arginine, a post-translational modification involved in cancer and embryonic development. However, the role of PRMT5 in T helper (Th) cell polarization and Th cell-mediated disease has not yet been elucidated. Here we report that PRMT5 is necessary for Th17 differentiation and EAE, via enhancement of cholesterol biosynthesis and activation of ROR-{gamma}t. PRMT5 additionally controls thymic and peripheral homeostasis in the CD4 Th cell life cycle, as well as iNK T and CD8 T cell development or maintenance, respectively. Overall, our two conditional PRMT5 KO models that selectively delete PRMT5 in all T cells (T-PRMT5{Delta}/{Delta}) or Th cells (iCD4-PRMT5{Delta}/{Delta}) unveil a crucial role for PRMT5 in T cell proliferation, Th17 responses and disease. These results point to Th PRMT5 and its downstream cholesterol biosynthesis pathway as promising therapeutic targets in Th17-mediated diseases.

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