| First Author | Hu P | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 40 | Pages | 33215-26 |
| PubMed ID | 22859305 | Mgi Jnum | J:191251 |
| Mgi Id | MGI:5461296 | Doi | 10.1074/jbc.M112.355594 |
| Citation | Hu P, et al. (2012) p38alpha protein negatively regulates T helper type 2 responses by orchestrating multiple T cell receptor-associated signals. J Biol Chem 287(40):33215-26 |
| abstractText | Mitogen-activated protein kinase p38alpha is a critical regulator of certain inflammatory diseases. However, its role in T helper type 2 (Th2) responses and allergic inflammation remains unknown. Here we show an increase in the production of interleukin-4 (IL-4) in p38alpha(-/-) CD4(+) T cells in response to antigen stimulation. p38alpha-deficient naive CD4(+) T cells preferentially differentiate into Th2 cells through increased endogenous production of IL-4. Consistent with those results, we also observed decreased expression of p38alpha during T helper cell differentiation. Furthermore, deficiency of p38alpha alters the balance in the expression of NFATc1 and NFATc2 under steady-state conditions and enhances the expression and nuclear translocation of NFATc1 in CD4(+) T cells upon antigen stimulation. Knockdown of NFATc1 significantly inhibits Th2 differentiation in p38alpha(-/-) T cells but not in p38alpha(+/-) T cells. p38alpha deficiency also inhibits the activation of Akt but enhances the activation of ERK in response to T cell receptor engagement without impacting IL-2/Stat5 signaling. In a model of ovalbumin-induced acute allergic airway inflammation, mice with induced deletion of p38alpha show elevated serum ovalbumin-specific IgE level, increased infiltration of eosinophils, and higher concentrations of Th2 cytokines including IL-4 and IL-5 in the bronchoalveolar lavage fluid relative to control mice. Taken together, p38alpha regulates multiple T cell receptor-associated signals and negatively influences Th2 differentiation and allergic inflammation. |
