期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 42, 期 9, 页码 2329-2342出版社
WILEY-BLACKWELL
DOI: 10.1002/eji.201142240
关键词
Epigenetics; IFN-; IL-17; SOCS3; Tc17; IFN-? cells
类别
资金
- Japanese Ministry of Education, Culture, Sports, Science, and Technology
- Japan Society for the Promotion of Science
- Ministry of Education, Culture, Sports, Science, and Technology (MEXT)
- Grants-in-Aid for Scientific Research [22300331] Funding Source: KAKEN
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-? 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-?-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-?-double producing CD8+ T (Tc17/IFN-?) 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 ROR?t. These findings elucidate the mechanisms underlying the conversion of Tc17 cells into Tc17/IFN-? cells. As these cells are known to have potent antitumor activities, manipulation of these conversion mechanisms for therapeutic tumor immunity may be possible.
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