| First Author | Sumitomo S | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 5 | Pages | 2351-9 |
| PubMed ID | 23904169 | Mgi Jnum | J:205814 |
| Mgi Id | MGI:5546481 | Doi | 10.4049/jimmunol.1202106 |
| Citation | Sumitomo S, et al. (2013) Transcription factor early growth response 3 is associated with the TGF-beta1 expression and the regulatory activity of CD4-positive T cells in vivo. J Immunol 191(5):2351-9 |
| abstractText | TGF-beta1 is an important anti-inflammatory cytokine, and several regulatory T cell (Treg) subsets including CD4(+)CD25(+)Foxp3(+) Tregs and Th3 cells have been reported to exert regulatory activity via the production of TGF-beta1. However, it has not yet been elucidated which transcription factor is involved in TGF-beta1 transcription. Early growth response 3 (Egr-3) is a zinc-finger transcription factor that creates and maintains T cell anergy. In this study, we found that Egr-3 induces the expression of TGF-beta1 in both murine and human CD4(+) T cells. Egr-3 overexpression in murine CD4(+) T cells induced the production of TGF-beta1 and enhanced the phosphorylation of STAT3, which is associated with TGF-beta1 transcription. Moreover, Egr-3 conferred Ag-specific regulatory activity on murine CD4(+) T cells. In collagen-induced arthritis and delayed-type hypersensitivity model mice, Egr-3-transduced CD4(+) T cells exhibited significant regulatory activity in vivo. In particular, the suppression of delayed-type hypersensitivity depended on TGF-beta1. In human tonsils, we found that CD4(+)CD25(-)CD45RO(-)lymphocyte activation gene 3 (LAG3)(-) T cells express membrane-bound TGF-beta1 in an EGR3-dependent manner. Gene-expression analysis revealed that CD4(+)CD25(-)CD45RO(-)LAG3(-) T cells are quite different from conventional CD4(+)CD25(+)Foxp3(+) Tregs. Intriguingly, the CD4(+)CD25(-)CD45RO(-)LAG3(-) T cells suppressed graft-versus-host disease in immunodeficient mice transplanted with human PBMCs. Our results suggest that Egr-3 is a transcription factor associated with TGF-beta1 expression and in vivo regulatory activity in both mice and humans. |
