title: CD73 is critical for the resolution of murine colonic inflammation.
abstract: CD73 is a glycosyl-phosphatidylinositol-(GPI-) linked membrane protein that catalyzes the extracellular dephosphorylation of adenosine monophosphate (AMP) to adenosine. Adenosine is a negative regulator of inflammation and prevents excessive cellular damage. We investigated the role of extracellular adenosine in the intestinal mucosa during the development of Dextran-Sulfate-Sodium-(DSS-)salt-induced colitis in mice that lack CD73 (CD73(-/-)) and are unable to synthesize extracellular adenosine. We have found that, compared to wild-type (WT) mice, CD73(-/-) mice are highly susceptible to DSS-induced colitis. CD73(-/-) mice exhibit pronounced weight loss, slower weight recovery, an increase in gut permeability, a decrease in expression of tight junctional adhesion molecules, as well as unresolved inflammation following the removal of DSS. Moreover, colonic epithelia in CD73(-/-) mice exhibited increased TLR9 expression, high levels of IL-1β and TNF-α, and constitutive activation of NF-κB. We conclude that CD73 expression in the colon is critical for regulating the magnitude and the resolution of colonic immune responses.
authors.affiliation: Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. msb76@cornell.edu
authors.forename: Margaret S
authors.initials: MS
authors.lastname: Bynoe
authors.forename: Adam T
authors.initials: AT
authors.lastname: Waickman
authors.forename: Deeqa A
authors.initials: DA
authors.lastname: Mahamed
authors.forename: Cynthia
authors.initials: C
authors.lastname: Mueller
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Mills
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Czopik
mesh_terms: D015720:5'-Nucleotidase / Q000172:deficiency / Q000378:metabolism*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003092:Colitis / Q000201:enzymology* / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D003106:Colon / Q000201:enzymology* / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D058851:GPI-Linked Proteins / Q000172:deficiency / Q000378:metabolism; D007249:Inflammation / Q000201:enzymology* / Q000473:pathology*; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000473:pathology; D053583:Interleukin-1beta / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000201:enzymology / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D010539:Permeability; D020127:Recovery of Function; D062725:Tight Junction Proteins / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation
chemical_list: D058851:GPI-Linked Proteins; D053583:Interleukin-1beta; D016328:NF-kappa B; D062725:Tight Junction Proteins; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; D017493:Leukocyte Common Antigens; D015720:5'-Nucleotidase; C548242:Nt5e protein, mouse