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Determining factors in T cell differentiation and survival include antigen recognition, but also the metabolic machinery that provides energy and biosynthetic molecules for cell building. Studies in patients with RA have yielded a disease\u2010specific metabolic signature, which enables naive CD4 T cells to differentiate into pro\u2010inflammatory helper T cells that are prone to invade into tissue and elicit inflammation through immunogenic cell death. A typifying property of RA CD4 T cells is the shunting of glucose away from glycolytic breakdown and mitochondrial processing toward the pentose phosphate pathway, favoring anabolic over catabolic reactions. Key defects have been localized to the mitochondria and the lysosome; including instability of mitochondrial DNA due to the lack of the DNA repair nuclease MRE11A and inefficient lysosomal tethering of AMPK due to deficiency of N\u2010myristoyltransferase 1 (NMT1). The molecular taxonomy of the metabolically reprogrammed RA T cells includes glycolytic enzymes (glucose\u20106\u2010phosphate dehydrogenase, phosphofructokinase), DNA repair molecules (MRE11A, ATM), regulators of protein trafficking (NMT1), and the membrane adapter protein TSK5. As the mechanisms determining abnormal T cell behavior in RA are unraveled, opportunities will emerge to interject autoimmune T cells by targeting their metabolic checkpoints.<\/jats:p>","DOI":"10.1111\/imr.12838","type":"journal-article","created":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T08:41:52Z","timestamp":1580114512000},"page":"177-187","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":182,"title":["Immunometabolism in the development of rheumatoid arthritis"],"prefix":"10.1111","volume":"294","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2230-9802","authenticated-orcid":false,"given":"Cornelia M.","family":"Weyand","sequence":"first","affiliation":[{"name":"Department of Medicine Stanford University Stanford CA USA"},{"name":"Department of Medicine Palo Alto Veterans Administration Healthcare System Palo Alto CA 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