PRMT5 in T helper lymphocytes is essential for cholesterol biosynthesis-mediated Th17 responses and autoimmunity
Cold Spring Harbor Laboratory, 2019
Online
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Zugriff:
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-γt. 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-PRMT5Δ/Δ) or Th cells (iCD4-PRMT5Δ/Δ) 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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PRMT5 in T helper lymphocytes is essential for cholesterol biosynthesis-mediated Th17 responses and autoimmunity
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Autor/in / Beteiligte Person: | Amici, Stephanie A. ; Webb, Lindsay M. ; Narvaez-Miranda, Janiret ; Kennemer, Austin ; Guerau-de-Arellano, Mireia ; Edell, Claudia ; Sengupta, Shouvonik |
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Veröffentlichung: | Cold Spring Harbor Laboratory, 2019 |
Medientyp: | unknown |
DOI: | 10.1101/792788 |
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