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De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells
- Source :
- Nature Medicine. November 1, 2014, Vol. 20 Issue 11, p1327, 9 p.
- Publication Year :
- 2014
-
Abstract
- Interleukin-17 (IL-17)-secreting T cells of the T helper 17 ([T.sub.H]17) lineage play a pathogenic role in multiple inflammatory and autoimmune conditions and thus represent a highly attractive target for therapeutic intervention. We report that inhibition of acetyl-CoA carboxylase 1 (ACC1) restrains the formation of human and mouse [T.sub.H]17 cells and promotes the development of anti-inflammatory Foxp[3.sup.+] regulatory T ([T.sub.reg]) cells. We show that [T.sub.H]17 cells, but not [T.sub.reg] cells, depend on ACC1-mediated de novo fatty acid synthesis and the underlying glycolytic-lipogenic metabolic pathway for their development. Although [T.sub.H]17 cells use this pathway to produce phospholipids for cellular membranes, [T.sub.reg] cells readily take up exogenous fatty acids for this purpose. Notably, pharmacologic inhibition or T cell-specific deletion of ACC1 not only blocks de novo fatty acid synthesis but also interferes with the metabolic flux of glucose-derived carbon via glycolysis and the tricarboxylic acid cycle. In vivo, treatment with the ACC-specific inhibitor soraphen A or T cell-specific deletion of ACC1 in mice attenuates [T.sub.H]17 cell-mediated autoimmune disease. Our results indicate fundamental differences between [T.sub.H]17 cells and [T.sub.reg] cells regarding their dependency on ACC1-mediated de novo fatty acid synthesis, which might be exploited as a new strategy for metabolic immune modulation of [T.sub.H]17 cell-mediated inflammatory diseases.<br />To develop from naive cells into distinct T cell lineages, activated T cells undergo a massive metabolic switch to cope with the demands of cell growth and multiple rounds of [...]
Details
- Language :
- English
- ISSN :
- 10788956
- Volume :
- 20
- Issue :
- 11
- Database :
- Gale General OneFile
- Journal :
- Nature Medicine
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.390562441