Dusp5 negatively regulates IL ‐33‐mediated eosinophil survival and function

Mitogen‐activated protein kinase ( MAPK ) activation controls diverse cellular functions including cellular survival, proliferation, and apoptosis. Tuning of MAPK activation is counter‐regulated by a family of dual‐specificity phosphatases ( DUSP s). IL ‐33 is a recently described cytokine that initiates Th2 immune responses through binding to a heterodimeric IL ‐33Rα ( ST 2L)/ IL ‐1α accessory protein ( IL ‐1 RA cP) receptor that coordinates activation of ERK and NF ‐κB pathways. We demonstrate here that DUSP 5 is expressed in eosinophils, is upregulated following IL‐33 stimulation and regulates IL ‐33 signaling. Dusp5 −/− mice have prolonged eosinophil survival and enhanced eosinophil effector functions following infection with the helminth Nippostrongylus brasiliensis . IL ‐33‐activated Dusp5 −/− eosinophils exhibit increased cellular ERK 1/2 activation and BCL ‐ X L expression that results in enhanced eosinophil survival. In addition, Dusp5 −/− eosinophils demonstrate enhanced IL ‐33‐mediated activation and effector functions. Together, these data support a role for DUSP 5 as a novel negative regulator of IL ‐33‐dependent eosinophil function and survival.