ERK1 is important for Th2 differentiation and development of experimental asthma.
FASEB J
; 26(5): 1934-45, 2012 May.
Article
in En
| MEDLINE
| ID: mdl-22262639
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Asthma
/
Cell Differentiation
/
Th2 Cells
/
Mitogen-Activated Protein Kinase 3
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
FASEB J
Journal subject:
BIOLOGIA
/
FISIOLOGIA
Year:
2012
Type:
Article
Affiliation country:
United States