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We are analyzing https://www.nature.com/articles/ni.3808.

Title:
Metabolic control of the scaffold protein TKS5 in tissue-invasive, proinflammatory T cells | Nature Immunology
Description:
Previous studies have defined a state of metabolic reprogramming in rheumatoid arthritis (RA) T cells. Here Weyand and colleagues show that the rewiring of cellular metabolism renders RA T cells tissue invasive, directly promoting disease-inducing effector functions. 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.
Website Age:
30 years and 10 months (reg. 1994-08-11).

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Keywords {🔍}

pubmed, article, google, scholar, cas, cells, central, cell, nature, arthritis, rheumatoid, nat, data, metabolic, control, supplementary, weyand, access, cdcdra, goronzy, content, tks, pyruvate, rev, biol, acid, med, immunol, immunity, figure, expression, shpxda, sem, cookies, information, immunology, fatty, metabolism, experiments, sirna, healthy, privacy, protein, lipid, patients, sci, mol, yang, human, rheumatology,

Topics {✒️}

nature portfolio journals permissions reprints nature portfolio privacy policy advertising social media author information authors nature+ nature 460 nature 499 nature development mann-whitney u-teat author correspondence mann-whitney u-test t-cell-targeted therapies affect ppar-γ expression ppar-γ expression levels received ip injections establish treg-cell function permissions springerlink instant access cd4+cd45ra+ifn-γ+ cd4+cd45ra+cd28+cd95+ dose response analysis o'sullivan specific tissue sites fatty acid synthase privacy invadopodia actin regulation paired t-test fatty acid remodeling src mediated assembly competing financial interests lipid mediator profiling scaffold protein tks5 intracellular ifn-γ content fat article shen citric acid cycle tks5 protein expression coronary artery disease nuclease mre11a induces directional cell migration t-lymphocyte crawling subscription content issue learn identify memory cd4+ article purchase t-cell aging

Schema {🗺️}

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         description:Previous studies have defined a state of metabolic reprogramming in rheumatoid arthritis (RA) T cells. Here Weyand and colleagues show that the rewiring of cellular metabolism renders RA T cells tissue invasive, directly promoting disease-inducing effector functions. 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.
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      headline:Metabolic control of the scaffold protein TKS5 in tissue-invasive, proinflammatory T cells
      description:Previous studies have defined a state of metabolic reprogramming in rheumatoid arthritis (RA) T cells. Here Weyand and colleagues show that the rewiring of cellular metabolism renders RA T cells tissue invasive, directly promoting disease-inducing effector functions. 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.
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