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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. ATPlopyruvatelo 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 proarthritogenic behavior. Thus, metabolic control of T cell locomotion provides new opportunities to interfere with T cell invasion into specific tissue sites.

SUBMITTER: Shen Y 

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

REPOSITORIES: biostudies-literature

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

Shen Yi Y   Wen Zhenke Z   Li Yinyin Y   Matteson Eric L EL   Hong Jison J   Goronzy Jörg J JJ   Weyand Cornelia M CM  

Nature immunology 20170724 9


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  ...[more]

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