title: CD73 is expressed by inflammatory Th17 cells in experimental autoimmune encephalomyelitis but does not limit differentiation or pathogenesis.
abstract: CD73 works together with CD39 to convert extracellular ATP to immunoregulatory adenosine, thus inhibiting inflammation. TGFβ-mediated CD73 expression on 'regulatory' Th17 cells limits their ability to eradicate tumors, similar to the immunosuppressive mechanism described for CD73 on Tregs. However, CD73 is also expressed on Th17 cells thought to be inflammatory in Crohn's disease. CD73 has previously been reported to contribute to inflammation in the central nervous system (CNS). In experimental autoimmune encephalomyelitis (EAE), we found that inflammatory cytokine-producing Th17 cells showed increased CD73 expression as disease progressed. We therefore hypothesized that CD73 could be important for limiting the expansion or pathogenic function of Th17 cells in autoimmune inflammation of the CNS. Surprisingly, EAE development was not enhanced or inhibited by CD73 deficiency; there was correspondingly no difference in induction of Th17-associated cytokines IL-17, IFNγ or GM-CSF or recruitment of either inflammatory or regulatory cells to the central nervous system. We confirmed that CD73 was similarly not required for differentiation of Th17 cells in vitro. These data show that while CD73 expression is regulated during EAE, this enzyme is not absolutely required to either promote or limit Th17 cell expansion or EAE severity.
authors.affiliation: Division of Rheumatology & Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Gerard
authors.initials: G
authors.lastname: Hernandez-Mir
authors.affiliation: Division of Rheumatology & Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Mandy J
authors.identifier: http://orcid.org/0000-0001-5029-1668
authors.initials: MJ
authors.lastname: McGeachy
mesh_terms: D015720:5'-Nucleotidase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002490:Central Nervous System / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology*; D007249:Inflammation / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000473:pathology*
chemical_list: D015415:Biomarkers; D015720:5'-Nucleotidase