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Gfi1, a transcriptional repressor, inhibits the induction of the T helper type 1 programme in activated CD 4 T cells
Author(s) -
Suzuki Junpei,
Maruyama Saho,
Tamauchi Hidekazu,
Kuwahara Makoto,
Horiuchi Mika,
Mizuki Masumi,
Ochi Mizuki,
Sawasaki Tatsuya,
Zhu Jinfang,
Yasukawa Masaki,
Yamashita Masakatsu
Publication year - 2016
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12580
Subject(s) - repressor , biology , transcription factor , immune system , microbiology and biotechnology , il 2 receptor , foxp3 , epigenetics , histone , transcriptional regulation , cellular differentiation , t cell , gene , immunology , genetics
Summary 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 CD 4 T cells. The activated Gfi1 ‐deficient CD 4 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 CD 4 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.