Mina, an Il4 repressor, controls T helper type 2 bias.
T helper type 2 (T(H)2) bias, which is the propensity of naive CD4(+) T cells to differentiate into interleukin 4 (IL-4)-secreting T(H)2 cells, is a genetic trait that affects susceptibility to infectious, autoimmune and allergic diseases. T(H)2 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 T(H)2 development. Here we identify Mina, a member of the jumonji C (JmjC) protein family, as a genetic determinant of T(H)2 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 T(H)2 bias.
Okamoto
Mariko
M
Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Japan.
Van Stry
Melanie
M
Chung
Linda
L
Koyanagi
Madoka
M
Sun
Xizhang
X
Suzuki
Yoshie
Y
Ohara
Osamu
O
Kitamura
Hiroshi
H
Hijikata
Atsushi
A
Kubo
Masato
M
Bix
Mark
M
D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D050990:GATA3 Transcription Factor / Q000378:metabolism; D006239:Haplotypes; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D050800:STAT6 Transcription Factor / Q000378:metabolism; D013045:Species Specificity; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*
D050990:GATA3 Transcription Factor; C512207:Mina53 protein, mouse; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D050800:STAT6 Transcription Factor; D015847:Interleukin-4