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This condition occurs in response to abdominal injury, gallstones, chronic alcohol consumption or, less frequently, the cause remains idiopathic. CD73 is a cell surface ecto\u20105\u2032\u2010nucleotidase that generates extracellular adenosine, which can contribute to resolution of inflammation by binding adenosine receptors on infiltrating immune cells. We hypothesized genetic deletion of CD73 would result in more severe pancreatitis due to decreased generation of extracellular adenosine. CD73 knockout (\n                    <jats:italic>CD73<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) and C57BL\/6 (wild type, WT) mice were used to evaluate the progression and response of caerulein\u2010induced acute and chronic pancreatitis. In response to caerulein\u2010mediated chronic or acute pancreatitis, WT mice display resolution of pancreatitis at earlier timepoints than\n                    <jats:italic>CD73<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. Using immunohistochemistry and analysis of single\u2010cell RNA\u2010seq (scRNA\u2010seq) data, we determined CD73 localization in chronic pancreatitis is primarily observed in mucin\/ductal cell populations and immune cells. In murine pancreata challenged with caerulein to induce acute pancreatitis, we compared\n                    <jats:italic>CD73<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    to WT mice and observed a significant infiltration of Ly6G+, MPO+, and Granzyme B+ cells in\n                    <jats:italic>CD73<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    compared to WT pancreata and we quantified a significant increase in acinar\u2010to\u2010ductal metaplasia demonstrating sustained metaplasia and inflammation in\n                    <jats:italic>CD73<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. Using neutrophil depletion in\n                    <jats:italic>CD73<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, we show neutrophil depletion significantly reduces metaplasia defined by CK19+ cells per field and significantly reduces acute pancreatitis. These data identify CD73 enhancers as a potential therapeutic strategy for patients with acute and chronic pancreatitis as adenosine generation and activation of adenosine receptors is critical to resolve persistent inflammation in the pancreas.\n                  <\/jats:p>","DOI":"10.1096\/fj.202201537r","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T07:41:55Z","timestamp":1670226115000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["<scp>CD73<\/scp>\n                    \u2010generated extracellular adenosine promotes resolution of neutrophil\u2010mediated tissue injury and restrains metaplasia in pancreatitis"],"prefix":"10.1096","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4272-6654","authenticated-orcid":false,"given":"Baylee J.","family":"O'Brien","sequence":"first","affiliation":[{"name":"Center for Perioperative Medicine, Department of 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