DELINEATING THE ROLE OF CALCINEURIN A ALPHA IN THE MAST CELL FCϵRI-MEDIATED IMMUNE RESPONSE
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Allergies are a health challenge resulting from excessive and inappropriate responses to innocuous antigens (allergens), and a key cellular player is the mast cell. Mast cell activation by allergen initiates a response through the FcϵRI culminating in the release of multiple inflammatory mediators. Calcineurin inhibitors have been used to treat allergies; however, there is a lack of understanding of the contributions of calcineurin isoforms. Knowledge of calcineurin isoforms may reveal specific targets to treat allergy. Therefore FcϵRI-mediated events were examined in mast cells from mice lacking calcineurin Aα. While appearing morphologically normal, the cells show decreased degranulation and release of cytokines and chemokines in vitro. Upon adoptive transfer into mice, the reduction in mediator release was detected in the early but not late phase response. The reduction in mediator release was associated with a reduction in the NF-κB signaling pathway. Thus, specifically blocking calcineurin Aα may reduce FcϵRI-mediated allergy.