Doherty, GlenBai, AipingHanidziar, DusanLonghi, Maria SerenaLawlor, GarrettPutheti, PrabhakarCsizmadia, EvaNowak, MartinaCheifetz, AdamMoss, AlanRobson, Simon2020-04-152012-10-29Doherty, G., A. Bai, D. Hanidziar, S.M. Longhi, G.O. Lawlor, P. Putheti, E Csizmadia, M. Nowak, A.S. Cheifetz, S.C. Robson, and A.C. Moss. 2012. CD73 Is a Phenotypic Marker of Effector Memory Th17 Cells in Inflammatory Bowel Disease. European Journal of Immunology 42, no. 11: 3062-3072.0014-2980http://nrs.harvard.edu/urn-3:HUL.InstRepos:42659693Purinergic signaling and associated ectonucleotidases, such as CD39 and CD73, have been implicated in the pathogenesis of inflammatory bowel disease (IBD). CD39 is known to be a Treg memory cell marker, and here we determine the phenotype and function of CD73+CD4+ T lymphocytes in patients with IBD. We describe elevated levels of CD73+CD4+ T cells in the peripheral blood and intestinal lamina propria of patients with active IBD. The functional phenotype of these CD73+CD4+ T cells was further determined by gene expression, ecto-enzymatic activity, and suppressive assays. Increased numbers of CD73+CD4+ T cells in the periphery and lamina propria were noted during active inflammation, which returned to baseline levels following anti-TNF treatment. Peripheral CD73+CD4+ T cells predominantly expressed CD45RO, and were enriched with IL-17A+ cells. The CD73+CD4+ cell population expressed higher levels of RORC, IL-17A, and TNF, and lower levels of FOXP3 and/or CD25, than CD73−CD4+ T cells. Expression of CD73 by peripheral CD4+ T cells was increased by TNF, and decreased by an anti-TNF monoclonal antibody (infliximab). In vitro, these peripheral CD73+CD4+ T cells did not suppress proliferation of CD25− effector cells, and expressed higher levels of pro-inflammatory markers. We conclude that the CD73+CD4+ T-cell population in patients with active IBD are enriched with cells with a T-helper type 17 phenotype, and could be used to monitor disease activity during treatment.en-USJournal Article2017-09-1420122020-04-1510.1002/eji.201242623