Insulin Sensitivity Controls Activity of Pathogenic CD4+ T Cells in Rheumatoid Arthritis.

ABSTRACT: Hyperinsulinemia connects obesity, and a poor lipid profile, with type 2 diabetes (T2D). Here, we investigated consequences of insulin exposure for T cell function in the canonical autoimmunity of rheumatoid arthritis (RA). We observed that insulin levels correlated with the glycolytic index of CD4+ cells but suppressed transcription of insulin receptor substrates, which was inversely related to insulin sensitivity. This connection between insulin levels and the glycolytic index was not seen in CD4+ cells of healthy controls. Exposure of CD4+ cells to insulin induced a senescent state recognized by cell cycle arrest and DNA content enrichment measured by flow cytometry. It also resulted in accumulation of DNA damage marker γH2AX. Insulin suppressed IFNγ production and induced the senescenc

SUBMITTER: Erlandsson MC 

PROVIDER: S-EPMC11674209 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature