The PP2A regulatory subunit PPP2R2A controls NAD⁺ biosynthesis to regulate T cell subset differentiation in systemic autoimmunity.

ABSTRACT: The protein phosphatase 2A (PP2A) regulatory subunit PPP2R2A is involved in the regulation of immune response. We report that lupus-prone mice with T cells deficient in PPP2R2A display less autoimmunity and nephritis. PPP2R2A deficiency promotes NAD⁺ biosynthesis through the nicotinamide riboside (NR)-directed salvage pathway in T cells. NR inhibits murine Th17 and promotes Treg cell differentiation, in vitro, by PΑRylating histone H1.2 and causing its reduced occupancy in the Foxp3 loci and increased occupancy in the Il17a loci, leading to increased Foxp3 and decreased Il17a transcription. NR treatment suppresses disease in MRL.lpr mice and restores NAD⁺-dependent poly [ADP-ribose] polymerase 1 (PARP1) activity in CD4 T cells from patients with systemic lupus erythem

SUBMITTER: Pan W 

PROVIDER: S-EPMC11414414 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature