| First Author | Huang CY | Year | 2012 |
| Journal | Eur J Immunol | Volume | 42 |
| Issue | 2 | Pages | 476-88 |
| PubMed ID | 22101742 | Mgi Jnum | J:180366 |
| Mgi Id | MGI:5306169 | Doi | 10.1002/eji.201041295 |
| Citation | Huang CY, et al. (2012) DUSP4 deficiency enhances CD25 expression and CD4(+) T-cell proliferation without impeding T-cell development. Eur J Immunol 42(2):476-88 |
| abstractText | The differentiation and activation of T cells are critically modulated by MAP kinases, which are in turn feed-back regulated by dual-specificity phosphatases (DUSPs) to determine the duration and magnitude of MAP kinase activation. DUSP4 (also known as MKP2) is a MAP kinase-induced DUSP member that is dynamically expressed during thymocyte differentiation. We generated DUSP4-deficient mice to study the function of DUSP4 in T-cell development and activation. Our results show that thymocyte differentiation and activation-induced MAP kinase phosphorylation were comparable between DUSP4-deficient and WT mice. Interestingly, activated DUSP4(-/-) CD4(+) T cells were hyperproliferative while DUSP4(-/-) CD8(+) T cells proliferated normally. Further mechanistic studies suggested that the hyperproliferation of DUSP4(-/-) CD4(+) T cells resulted from enhanced CD25 expression and IL-2 signaling through increased STAT5 phosphorylation. Immunization of DUSP4(-/-) mice recapitulated the T-cell hyperproliferation phenotype in antigen recall responses, while the profile of Th1/Th2-polarized antibody production was not altered. Overall, these results suggest that other DUSPs may compensate for DUSP4 deficiency in T-cell development, MAP kinase regulation, and Th1/Th2-mediated antibody responses. More importantly, our data indicate that DUSP4 suppresses CD4(+) T-cell proliferation through novel regulations in STAT5 phosphorylation and IL-2 signaling. |
