T helper type 2 (T_H2) bias, which is the propensity of naive CD4~+ T cells to differentiate into interleukin 4 (IL-4)-secreting T_H2 cells, is a genetic trait that affects susceptibility to infectious, autoimmune and allergic diseases. T_H2 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_h2 development. Here we identify Mina, a member of the jumonji C (JmjC) protein family, as a genetic determinant of T_H2 bias. Mina specifically bound to and repressed the II4 promoter. Mina overexpression in transgenic mice impaired II4 expression, whereas its knockdown in primary CD4~+ T cells led to II4 derepression. Our findings collectively provide mechanistic insight into an II4-regulatory pathway that controls helper T cell differentiation and genetic variation in T_H2 bias.
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