Mina, an Il4 repressor, controls T helper type 2 bias

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.