DUSP10 constrains innate IL-33-mediated cytokine production in ST2hi memory-type pathogenic Th2 cells

Nat Commun. 2018 Oct 12;9(1):4231. doi: 10.1038/s41467-018-06468-8.


ST2hi memory-type Th2 cells are identified as a pathogenic subpopulation in eosinophilic airway inflammation. These ST2hi pathogenic Th2 cells produce large amount of IL-5 upon T cell receptor stimulation, but not in response to IL-33 treatment. By contrast, IL-33 alone induces cytokine production in ST2+ group 2 innate lymphoid cells (ILC2). Here we show that a MAPK phosphatase Dusp10 is a key negative regulator of IL-33-induced cytokine production in Th2 cells. In this regard, Dusp10 is expressed by ST2hi pathogenic Th2 cells but not by ILC2, and Dusp10 expression inhibits IL-33-induced cytokine production. Mechanistically, this inhibition is mediated by DUSP10-mediated dephosphorylation and inactivation of p38 MAPK, resulting in reduced GATA3 activity. The deletion of Dusp10 renders ST2hi Th2 cells capable of producing IL-5 by IL-33 stimulation. Our data thus suggest that DUSP10 restricts IL-33-induced cytokine production in ST2hi pathogenic Th2 cells by controlling p38-GATA3 activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Chromatin Immunoprecipitation
  • Cytokines / metabolism*
  • Dual-Specificity Phosphatases / genetics
  • Dual-Specificity Phosphatases / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • GATA3 Transcription Factor / metabolism
  • Humans
  • Immunoblotting
  • Interleukin-33 / pharmacology*
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Real-Time Polymerase Chain Reaction
  • Th2 Cells / drug effects*
  • Th2 Cells / metabolism*
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Cytokines
  • GATA3 Transcription Factor
  • Interleukin-33
  • p38 Mitogen-Activated Protein Kinases
  • Dusp10 protein, mouse
  • Dual-Specificity Phosphatases