| First Author | Iwasaki Y | Year | 2013 |
| Journal | Eur J Immunol | Volume | 43 |
| Issue | 4 | Pages | 1063-73 |
| PubMed ID | 23349024 | Mgi Jnum | J:195056 |
| Mgi Id | MGI:5476376 | Doi | 10.1002/eji.201242942 |
| Citation | Iwasaki Y, et al. (2013) Egr-2 transcription factor is required for Blimp-1-mediated IL-10 production in IL-27-stimulated CD4(+) T cells. Eur J Immunol 43(4):1063-73 |
| abstractText | Interleukin-27 (IL-27) suppresses immune responses through inhibition of the development of IL-17 producing Th17 cells and induction of IL-10 production. We previously showed that forced expression of early growth response gene 2 (Egr-2), a transcription factor required for T-cell anergy induction, induces IL-10 and lymphocyte activation gene 3 expression and confers regulatory activity on CD4(+) T cells in vivo. Here, we evaluated the role of Egr-2 in IL-27-induced IL-10 production. Among various IL-10-inducing factors, only IL-27 induced high levels of Egr-2 and lymphocyte activation gene 3 expression. Intriguingly, IL-27 failed to induce IL-10 in Egr-2-deficient T cells. IL-27-mediated induction of Prdm1 that codes B lymphocyte induced maturation protein-1, a transcriptional regulator important for IL-10 production in CD4(+) T cells, was also impaired in the absence of Egr-2. Although IL-27-mediated IL-10 induction was dependent on both STAT1 and STAT3, only STAT3 was required for IL-27-mediated Egr-2 induction. These results suggest that IL-27 signal transduction through Egr-2 and B lymphocyte induced maturation protein-1 plays an important role in IL-10 production. Furthermore, Egr-2-deficient CD4(+) T cells showed dysregulated production of IFN-gamma and IL-17 in response to IL-27 stimulation. Therefore, Egr-2 may play key roles in controlling the balance between regulatory and effector cytokines. |
