| First Author | Holmes DA | Year | 2015 |
| Journal | EMBO J | Volume | 34 |
| Issue | 2 | Pages | 218-35 |
| PubMed ID | 25398911 | Mgi Jnum | J:218203 |
| Mgi Id | MGI:5616979 | Doi | 10.15252/embj.201489456 |
| Citation | Holmes DA, et al. (2015) Dusp5 negatively regulates IL-33-mediated eosinophil survival and function. EMBO J 34(2):218-35 |
| abstractText | 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 (DUSPs). IL-33 is a recently described cytokine that initiates Th2 immune responses through binding to a heterodimeric IL-33Ralpha (ST2L)/IL-1alpha accessory protein (IL-1RAcP) receptor that coordinates activation of ERK and NF-kappaB pathways. We demonstrate here that DUSP5 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 ERK1/2 activation and BCL-XL 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 DUSP5 as a novel negative regulator of IL-33-dependent eosinophil function and survival. |
