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

EMBO J. 2015 Jan 13;34(2):218-35. doi: 10.15252/embj.201489456. Epub 2014 Nov 14.


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-33Rα (ST2L)/IL-1α accessory protein (IL-1RAcP) receptor that coordinates activation of ERK and NF-κB 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.

Keywords: BCL‐XL; dual‐specificity phosphatase 5; eosinophil survival.

MeSH terms

  • Animals
  • Blotting, Western
  • Cells, Cultured
  • DNA-Binding Proteins / physiology
  • Dual-Specificity Phosphatases / physiology*
  • Enzyme-Linked Immunosorbent Assay
  • Eosinophils / cytology
  • Eosinophils / drug effects
  • Eosinophils / immunology*
  • Eosinophils / parasitology
  • Female
  • Humans
  • Interleukin-33
  • Interleukins / pharmacology*
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / parasitology
  • Mice
  • Mice, Knockout
  • Nippostrongylus / pathogenicity
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Strongylida Infections / drug therapy
  • Strongylida Infections / immunology*
  • Strongylida Infections / mortality
  • Strongylida Infections / parasitology


  • DNA-Binding Proteins
  • Il33 protein, mouse
  • Interleukin-33
  • Interleukins
  • RNA, Messenger
  • Rag2 protein, mouse
  • Dual-Specificity Phosphatases
  • Dusp5 protein, mouse