Mina53, an IL4 repressor controlling TH2-bias (136.42)

• Published in: The Journal of immunology (1950) 2009-04, Vol.182 (1_Supplement), p.136-136.42
• Main Authors: Van Stry, Melanie, Okamoto, Mariko, Koyanagi, Madoka, Chung, Linda, Suzuki, Yoshie, Ohara, Osamu, Kitamura, Hiroshi, Hijikata, Atsushi, Tamari, Mayumi, Kubo, Masato, Bix, Mark
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.182.Supp.136.42

The naïve CD4 T helper (TH) cell can differentiate into several effector TH subsets, depending on the host-pathogen environment. TH1 cells, which express high levels of the cytokine IFNγ, are essential for clearance of intracellular pathogens, while TH2 cells, which express high levels of IL-4, are required for responses to extracellular pathogens. TH2-bias, which occurs when a naïve T cell preferentially differentiates to a TH2 cell, is a genetic trait impacting infectious, autoimmune, and allergic disease susceptibility. Previous studies in our laboratory have identified a quantitative trait locus that regulates TH2 bias in mice (Dice1.2). Here, we have identified Mina53, a JmjC family member, as the genetic determinant of Dice1.2. Mina53 specifically represses transcription from the Il4 promoter in transient reporter assays, while over-expression of Mina53 converts TH2 bias from high to low. Moreover, Mina53 binds to the proximal Il4 promoter, and this binding requires an interaction between Mina53 and nuclear factor of activated T cells (NFAT), a key regulator of cytokine expression. Taken together, these data provide mechanistic insight into the Il4 regulatory pathway controlling effector T cell differentiation and account, in part, for genetic variation in TH2 bias.