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Starting in the early \u201890s, however, lactate has begun to be recognized as an active molecule capable of modulating the immune response. Inflammatory sites, including in rheumatoid arthritis (RA) synovitis, are characterized by the accumulation of lactate, which is partly responsible for the establishment of an acidic environment. We have recently reported that T cells sense lactate via the expression of specific transporters, leading to inhibition of their motility. Importantly, this \u201cstop migration signal\u201d is dependent upon lactate's interference with intracellular metabolic pathways, specifically glycolysis. Furthermore, lactate promotes the switch of CD4<jats:sup>+<\/jats:sup> T cells to an IL\u201017<jats:sup>+<\/jats:sup> subset, and reduces the cytolytic capacity of CD8<jats:sup>+<\/jats:sup> T cells. These phenomena might be responsible for the formation of ectopic lymphoid structures and autoantibody production in inflammatory sites such as in RA synovitis, Sjogren syndrome salivary glands, and multiple sclerosis plaques. Here, we review the roles of lactate in the modulation of the inflammatory immune response.<\/jats:p>","DOI":"10.1002\/eji.201646477","type":"journal-article","created":{"date-parts":[[2016,11,24]],"date-time":"2016-11-24T15:17:50Z","timestamp":1480000670000},"page":"14-21","source":"Crossref","is-referenced-by-count":228,"title":["Lactate at the crossroads of metabolism, inflammation, and autoimmunity"],"prefix":"10.1002","volume":"47","author":[{"given":"Valentina","family":"Pucino","sequence":"first","affiliation":[{"name":"William Harvey Research Institute Barts and The London School of Medicine &amp; Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Bombardieri","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute Barts and The London School of Medicine &amp; Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Costantino","family":"Pitzalis","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute Barts and The London School of Medicine &amp; Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Mauro","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute Barts and The London School of Medicine &amp; Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,12,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.04.005"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.05.035"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1242454"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00001"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.05.004"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3152"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-030409-101212"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2012.01.010"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.02.029"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-015-2070-4"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032712-095956"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/0961203310373109"},{"key":"e_1_2_9_14_1","first-page":"17","article-title":"T\u2010cell metabolism in autoimmune disease","volume":"11","author":"Yang Z.","year":"2015","journal-title":"Arthritis Res. 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