Metabolic control of the scaffold protein TKS5 in tissue-invasive, proinflammatory T cells.

ABSTRACT: Pathogenic T cells in individuals with rheumatoid arthritis (RA) infiltrate non-lymphoid tissue sites, maneuver through extracellular matrix and form lasting inflammatory microstructures. Here we found that RA T cells abundantly express the podosome scaffolding protein TKS5, which enables them to form tissue-invasive membrane structures. TKS5 overexpression was regulated by the intracellular metabolic environment of RA T cells-specifically, by reduced glycolytic flux that led to deficiencies in ATP and pyruvate. ATP^lopyruvate^lo conditions triggered fatty acid biosynthesis and the formation of cytoplasmic lipid droplets. Restoration of pyruvate production or inhibition of fatty acid synthesis corrected the tissue-invasiveness of RA T cells in vivo and reversed their pr

SUBMITTER: Shen Y 

PROVIDER: S-EPMC5568495 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature