Regulation of autoimmune disease progression by Pik3ip1 through metabolic reprogramming in T cells and therapeutic implications.

ABSTRACT: Metabolic alterations could profoundly affect immune functions and influence the progression and outcome of autoimmune diseases. However, the detailed mechanisms and their therapeutic potential remain to be defined. Here, we show that phosphatidylinositide 3-kinase interacting protein 1 (Pik3ip1), a newly identified negative immune regulator, is notably down-regulated in several major autoimmune diseases through a previously unidentified mechanism mediated by interleukin-21/p38 mitogen-activated protein kinase/a disintegrin and metalloprotease-17 (ADAM17) pathway. Down-regulation of Pik3ip1 in T cells causes a major metabolic shift from oxidative phosphorylation toward aerobic glycolysis, leading to their overactivation and aggressive disease progression in experimental autoimmune encephal

SUBMITTER: Xie W 

PROVIDER: S-EPMC9524833 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature