| First Author | Yang XO | Year | 2008 |
| Journal | Immunity | Volume | 29 |
| Issue | 1 | Pages | 44-56 |
| PubMed ID | 18585065 | Mgi Jnum | J:137851 |
| Mgi Id | MGI:3803058 | Doi | 10.1016/j.immuni.2008.05.007 |
| Citation | Yang XO, et al. (2008) Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity 29(1):44-56 |
| abstractText | Regulatory T (Treg) and T helper 17 (Th17) cells were recently proposed to be reciprocally regulated during differentiation. To understand the underlying mechanisms, we utilized a Th17 reporter mouse with a red fluorescent protein (RFP) sequence inserted into the interleukin-17F (IL-17F) gene. Using IL-17F-RFP together with a Foxp3 reporter, we found that the development of Th17 and Foxp3(+) Treg cells was associated in immune responses. Although TGF-beta receptor I signaling was required for both Foxp3 and IL-17 induction, SMAD4 was only involved in Foxp3 upregulation. Foxp3 inhibited Th17 differentiation by antagonizing the function of the transcription factors RORgammat and ROR*. In contrast, IL-6 overcame this suppressive effect of Foxp3 and, together with IL-1, induced genetic reprogramming in Foxp3(+) Treg cells. STAT3 regulated Foxp3 downregulation, whereas STAT3, RORgamma, and ROR* were required for IL-17 expression in Treg cells. Our data demonstrate molecular antagonism and plasticity of Treg and Th17 cell programs. |
