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Recent studies have found that peripheral hematopoietic progenitor cells contribute to type 2 cytokine\u2013mediated inflammation through their enhanced ability to develop into mast cells. In this study, we show that carbonic anhydrase (Car) enzymes are up-regulated in type 2\u2013associated progenitor cells and demonstrate that Car enzyme inhibition is sufficient to prevent mouse mast cell responses and inflammation after Trichinella spiralis infection or the induction of food allergy\u2013like disease. Further, we used CRISPR\/Cas9 technology and illustrate that genetically editing Car1 is sufficient to selectively reduce mast cell development. Finally, we demonstrate that Car enzymes can be targeted to prevent human mast cell development. Collectively, these experiments identify a previously unrecognized role for Car enzymes in regulating mast cell lineage commitment and suggest that Car enzyme inhibitors may possess therapeutic potential that can be used to treat mast cell\u2013mediated inflammation.<\/jats:p>","DOI":"10.1084\/jem.20151739","type":"journal-article","created":{"date-parts":[[2016,8,15]],"date-time":"2016-08-15T14:07:30Z","timestamp":1471270050000},"page":"1663-1673","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":32,"title":["Carbonic anhydrase enzymes regulate mast cell\u2013mediated inflammation"],"prefix":"10.1084","volume":"213","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3884-2612","authenticated-orcid":false,"given":"Everett K.","family":"Henry","sequence":"first","affiliation":[{"name":"Center for Immunity and Inflammation, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ 07103 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