title: Characterization of human CD39+ Th17 cells with suppressor activity and modulation in inflammatory bowel disease.
abstract: Induced regulatory T-cells (iT-reg) and T helper type 17 (Th17) in the mouse share common CD4 progenitor cells and exhibit overlapping phenotypic and functional features. Here, we show that human Th17 cells endowed with suppressor activity (supTh17) can be derived following exposure of iT-reg populations to Th17 polarizing conditions. In contrast to "pathogenic" Th17, supTh17 display immune suppressive function and express high levels of CD39, an ectonucleotidase that catalyzes the conversion of pro-inflammatory extracellular nucleotides ultimately generating nucleosides. Accordingly, supTh17 exhibit nucleoside triphosphate diphosphohydrolase activity, as demonstrated by the efficient generation of extracellular AMP, adenosine and other purine derivatives. In addition supTh17 cells are resistant to the effects of adenosine as result of the low expression of the A2A receptor and accelerated adenosine catalysis by adenosine deaminase (ADA). These supTh17 can be detected in the blood and in the lamina propria of healthy subjects. However, these supTh17 cells are diminished in patients with Crohn's disease. In summary, we describe a human Th17 subpopulation with suppressor activity, which expresses high levels of CD39 and consequently produces extracellular adenosine. As these uniquely suppressive CD39+ Th17 cells are decreased in patients with inflammatory bowel disease, our findings might have implications for the development of novel anti-inflammatory therapeutic approaches in these and potentially other immune disorders.
authors: Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, United States of America ; Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, London, United Kingdom.
authors: Maria Serena
authors: MS
authors: Longhi
authors: Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, United States of America.
authors: Alan
authors: A
authors: Moss
authors: Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, United States of America.
authors: Aiping
authors: A
authors: Bai
authors: Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, United States of America.
authors: Yan
authors: Y
authors: Wu
authors: Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, United States of America.
authors: Huang
authors: H
authors: Huang
authors: Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, United States of America.
authors: Adam
authors: A
authors: Cheifetz
authors: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America.
authors: Francisco J
authors: FJ
authors: Quintana
authors: Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, United States of America.
authors: Simon C
authors: SC
authors: Robson
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D001081:Apyrase / Q000276:immunology*; D003424:Crohn Disease / Q000276:immunology* / Q000473:pathology*; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology*
chemical_list: D015703:Antigens, CD; D001081:Apyrase; C067869:CD39 antigen