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Publication : Carbonic anhydrase enzymes regulate mast cell-mediated inflammation.

First Author  Henry EK Year  2016
Journal  J Exp Med Volume  213
Issue  9 Pages  1663-73
PubMed ID  27526715 Mgi Jnum  J:236724
Mgi Id  MGI:5806994 Doi  10.1084/jem.20151739
Citation  Henry EK, et al. (2016) Carbonic anhydrase enzymes regulate mast cell-mediated inflammation. J Exp Med 213(9):1663-73
abstractText  Type 2 cytokine responses are necessary for the development of protective immunity to helminth parasites but also cause the inflammation associated with allergies and asthma. Recent studies have found that peripheral hematopoietic progenitor cells contribute to type 2 cytokine-mediated 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-associated 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-like 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-mediated inflammation.
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