Gfi1, a transcriptional repressor, inhibits the induction of the T helper type 1 programme in activated CD4 T cells
| Autor: | Junpei Suzuki, Masakatsu Yamashita, Mika Horiuchi, Makoto Kuwahara, Masumi Mizuki, Mizuki Ochi, Saho Maruyama, Tatsuya Sawasaki, Masaki Yasukawa, Hidekazu Tamauchi, Jinfang Zhu |
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| Rok vydání: | 2016 |
| Předmět: |
CD4-Positive T-Lymphocytes
0301 basic medicine Cellular differentiation Immunology Gene Expression Core Binding Factor Alpha 1 Subunit Mice Transgenic Biology Lymphocyte Activation Methylation Histones Interferon-gamma Mice 03 medical and health sciences Interleukin 21 0302 clinical medicine Immune system Animals Immunology and Allergy Cytotoxic T cell IL-2 receptor Transcription factor Histone Demethylases Mice Knockout ZAP70 Lymphokine Cell Differentiation Original Articles Th1 Cells Molecular biology DNA-Binding Proteins 030104 developmental biology Cytokines T-Box Domain Proteins Protein Binding Transcription Factors 030215 immunology |
| Zdroj: | Immunology. 147:476-487 |
| ISSN: | 0019-2805 |
| DOI: | 10.1111/imm.12580 |
| Popis: | A transcriptional repressor Gfi1 promotes T helper type 2 (Th2) cell development and inhibits Th17 and inducible regulatory T‐cell differentiation. However, the role of Gfi1 in regulating Th1 cell differentiation and the Th1‐type immune response remains to be investigated. We herein demonstrate that Gfi1 inhibits the induction of the Th1 programme in activated CD4 T cells. The activated Gfi1‐deficient CD4 T cells spontaneously develop into Th1 cells in an interleukin‐12‐ and interferon‐γ‐independent manner. The increase of Th1‐type immune responses was confirmed in vivo in Gfi1‐deficient mice using a murine model of nickel allergy and delayed‐type hypersensitivity (DTH). The expression levels of Th1‐related transcription factors were found to increase in Gfi1‐deficient activated CD4 T cells. Tbx21, Eomes and Runx2 were identified as possible direct targets of Gfi1. Gfi1 binds to the Tbx21, Eomes and Runx2 gene loci and reduces the histone H3K4 methylation levels in part by modulating Lsd1 recruitment. Together, these findings demonstrate a novel regulatory role of Gfi1 in the regulation of the Th1‐type immune response. |
| Databáze: | OpenAIRE |
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