論文 - 詳細
RRC ID | 17575 |
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著者 | Satoh T, Tajima M, Wakita D, Kitamura H, Nishimura T. |
タイトル | The development of IL-17/IFN-γ-double producing CTLs from Tc17 cells is driven by epigenetic suppression of Socs3 gene promoter. |
ジャーナル | Eur J Immunol |
Abstract |
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-γ 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-γ-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-γ-double producing CD8(+) T (Tc17/IFN-γ) 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 RORγt. These findings elucidate the mechanisms underlying the conversion of Tc17 cells into Tc17/IFN-γ cells. As these cells are known to have potent antitumor activities, manipulation of these conversion mechanisms for therapeutic tumor immunity may be possible. |
巻・号 | 42(9) |
ページ | 2329-42 |
公開日 | 2012-9-1 |
DOI | 10.1002/eji.201142240 |
PMID | 22674086 |
MeSH | Animals Autoimmune Diseases / genetics Autoimmune Diseases / immunology Autoimmune Diseases / metabolism CD8-Positive T-Lymphocytes / immunology* Cell Differentiation / genetics Cell Differentiation / immunology Epigenomics / methods Immunotherapy / methods Inflammation / genetics Inflammation / immunology Inflammation / metabolism Interferon-gamma / biosynthesis* Interferon-gamma / genetics* Interferon-gamma / immunology Interleukin-12 / genetics Interleukin-12 / immunology Interleukin-12 / metabolism Interleukin-17 / biosynthesis* Interleukin-17 / genetics* Interleukin-17 / immunology Mice Mice, Inbred C57BL Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics Nuclear Receptor Subfamily 1, Group F, Member 3 / immunology Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism Promoter Regions, Genetic / genetics* Promoter Regions, Genetic / immunology Suppressor of Cytokine Signaling 3 Protein Suppressor of Cytokine Signaling Proteins / deficiency Suppressor of Cytokine Signaling Proteins / genetics* Suppressor of Cytokine Signaling Proteins / immunology T-Lymphocyte Subsets / immunology |
IF | 4.404 |
引用数 | 30 |
WOS 分野 | IMMUNOLOGY |
リソース情報 | |
実験動物マウス | RBRC00144 |