MINA an IL-4 repressor controls TH2 bias

摘要

T helper-2 (TH2)-bias, the propensity of naive CD4⁺ T cells to differentiate into interleukin 4 (IL-4) secreting TH2 cells, is a genetic trait impacting infectious, autoimmune and allergic disease susceptibility. TH2-bias correlates with the amount of IL-4 initially secreted by newly activated TH cells that feeds back positively through the IL-4R-STAT6-GATA3 pathway to drive TH2 development. Here, we identify Mina, a JmjC family member, as a genetic determinant of TH2-bias. Mina specifically bound to and repressed the Il4 promoter. Mina overexpression in transgenic mice impaired Il4 expression, while its knockdown in primary CD4⁺ T cells led to Il4 derepression. Together, these findings provide mechanistic insight into an Il4 regulatory pathway controlling TH differentiation and genetic variation in TH2-bias.