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Carbonic anhydrase enzymes regulate mast cell-mediated immunity to Trichinella spiralis

Authors :
Mark C Siracusa
Everett K Henry
Chandler B Sy
Juan M. Inclan-Rico
Source :
The Journal of Immunology. 196:134.8-134.8
Publication Year :
2016
Publisher :
The American Association of Immunologists, 2016.

Abstract

Type 2 cytokine responses are necessary for the development of protective immunity to helminth parasites but also cause the detrimental inflammation associated with allergies and asthma. Recent studies have found that peripheral hematopoietic progenitor cell populations contribute to type 2 cytokine-mediated inflammation through their enhanced ability to develop into mast cells. Here we identify that carbonic anhydrase (Car) enzymes are upregulated in type 2-asscoaited progenitor cells and demonstrate that Car enzyme inhibition was sufficient to prevent murine mast cell development, type 2 cytokine-mediated inflammation and protective immunity to Trichinella spiralis. Moreover, we show that Car enzyme inhibition was also sufficient to prevent intestinal mast cell responses in a murine model of food allergy-like disease. Finally, we performed translational studies and demonstrated that Car enzymes can be targeted with an FDA-approved inhibitor to prevent human mast cell development. Collectively these studies identify a previously unrecognized role for Car enzymes in regulating mast cell lineage commitment and suggest that FDA-approved Car enzyme inhibitors may possess additional off-label therapeutic potential that can be employed to treat mast cell-mediated inflammation.

Subjects

Subjects :
Immunology
Immunology and Allergy

Details

ISSN :
15506606 and 00221767
Volume :
196
Database :
OpenAIRE
Journal :
The Journal of Immunology
Accession number :
edsair.doi...........e0a986756d1e5f3c58719252ada791c1
Full Text :
https://doi.org/10.4049/jimmunol.196.supp.134.8