RRC ID 17575
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