Article abstract
Nature Immunology 10, 872 - 879 (2009)
Published online: 28 June 2009 | Corrected online: 5 July 2009 | doi:10.1038/ni.1747
Mina, an Il4 repressor, controls T helper type 2 bias
Mariko Okamoto1,5, Melanie Van Stry2,5, Linda Chung2, Madoka Koyanagi2, Xizhang Sun3, Yoshie Suzuki1, Osamu Ohara4, Hiroshi Kitamura4, Atsushi Hijikata4, Masato Kubo1 & Mark Bix2
Abstract
T helper type 2 (TH2) bias, which is the propensity of naive CD4+ T cells to differentiate into interleukin 4 (IL-4)-secreting TH2 cells, is a genetic trait that affects susceptibility to infectious, autoimmune and allergic diseases. TH2 bias correlates with the amount of IL-4 initially secreted by newly activated helper T cells that feeds back positively through the pathway of the IL-4 receptor and the transcription factors STAT6 and GATA-3 to drive TH2 development. Here we identify Mina, a member of the jumonji C (JmjC) protein family, as a genetic determinant of TH2 bias. Mina specifically bound to and repressed the Il4 promoter. Mina overexpression in transgenic mice impaired Il4 expression, whereas its knockdown in primary CD4+ T cells led to Il4 derepression. Our findings collectively provide mechanistic insight into an Il4-regulatory pathway that controls helper T cell differentiation and genetic variation in TH2 bias.
- Laboratory for Signal Network, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama, Japan.
- Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
- Department of Immunology, University of Washington, Seattle, Washington, USA.
- Laboratory for Immunogenomics, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama, Japan.
- These authors contributed equally to this work.
Correspondence to: Mark Bix2 e-mail: mark.bix@stjude.org
Correspondence to: Masato Kubo1 e-mail: raysolfc@rcai.riken.jp
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