ERK1 is important for Th2 differentiation and development of experimental asthma

FASEB J. 2012 May;26(5):1934-45. doi: 10.1096/fj.11-196477. Epub 2012 Jan 18.


The ERK1/2 signaling pathway regulates a variety of T-cell functions. We observed dynamic changes in the expression of ERK1/2 during T-helper cell differentiation. Specifically, the expression of ERK1/2 was decreased and increased by IL-12 and IL-4, respectively. To address this subject further, we examined the specific role of ERK1 in Th2 differentiation and development of experimental asthma using ERK1(-/-) mice. ERK1(-/-) mice were unable to mount airway inflammation and hyperreactivity in two different models of asthma, acute and chronic. ERK1(-/-) mice had reduced expression of Th2 cytokines IL-4 and IL-5 but not IL-17A or IFN-γ. They had reduced levels of allergen-specific IgE and blood eosinophils. T cells from immunized ERK1(-/-) mice manifested reduced proliferation in response to the sensitizing allergen. ERK1(-/-) T cells had reduced and short-lived expression of JunB following TCR stimulation, which likely contributed to their impaired Th2 differentiation. Immunized ERK1(-/-) mice showed reduced numbers of CD44(high) CD4 T cells in the spleen. In vitro studies demonstrated that Th2 but not Th1 cells from ERK1(-/-) mice had reduced numbers of CD44(high) cells. Finally, CD4 T cells form ERK1(-/-) mice expressed higher levels of BIM under growth factor-deprived conditions and reduced Mcl-1 on stimulation. As a result, the survival of CD4 T cells, especially CD44(high) Th2 cells, was much reduced in ERK1(-/-) mice. We conclude that ERK1 plays a nonredundant role in Th2 differentiation and development of experimental asthma. ERK1 controls Th2 differentiation and survival through its effect on JunB and BIM, respectively.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Asthma / enzymology
  • Asthma / pathology*
  • CD4 Lymphocyte Count
  • Cell Differentiation*
  • Cell Proliferation
  • Eosinophils / cytology
  • Flow Cytometry
  • Humans
  • Mice
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Th2 Cells / cytology*


  • Mitogen-Activated Protein Kinase 3