| First Author | Satoh T | Year | 2012 |
| Journal | Eur J Immunol | Volume | 42 |
| Issue | 9 | Pages | 2329-42 |
| PubMed ID | 22674086 | Mgi Jnum | J:347201 |
| Mgi Id | MGI:6511433 | Doi | 10.1002/eji.201142240 |
| Citation | Satoh T, et al. (2012) The development of IL-17/IFN-gamma-double producing CTLs from Tc17 cells is driven by epigenetic suppression of Socs3 gene promoter. Eur J Immunol 42(9):2329-42 |
| abstractText | The plasticity of T lymphocytes induced by epigenetic modifications of gene promoters may play a pivotal role in controlling their effector functions, which are sometimes causally associated with immune disorders. IL -17-producing T cells, which induce type 17 immune responses, are newly identified pathogenic effector cells. The type 1 signature cytokine IFN-gamma strongly inhibits their differentiation, indicating a mutually exclusive relationship between type 17- and type 1-immune responses. However, many reports indicate the presence of a unique IL-17/IFN-gamma-double producing T-cell subset in various inflammatory settings, although the mechanisms responsible for their development and their precise functions remain unclear. Here, we demonstrate that IL-12 permits the conversion of mouse IL-17-producing CD8(+) T (Tc17) cells to IL-17/IFN-gamma-double producing CD8(+) T (Tc17/IFN-gamma) cells, and that this conversion is due to repressive epigenetic modifications of Socs3 gene promoters. Moreover, we show that SOCS3 strongly regulates the capability of Tc17 cells to produce IL-17, in addition to regulating the expression of the type 17-master regulator RORgammat. These findings elucidate the mechanisms underlying the conversion of Tc17 cells into Tc17/IFN-gamma cells. As these cells are known to have potent antitumor activities, manipulation of these conversion mechanisms for therapeutic tumor immunity may be possible. |
