We recently identified Mina53 as a Th2-bias regulatory gene that acts (at least in part) via a progenitor T helper cell-intrinsic IL4 regulatory activity. Mina53 belongs to the Jmj protein family, multiple members of which possess histone demethylase activity. In preliminary studies we have discovered that Mina53 is specifically recruited to the IL4 promoter, is necessary and sufficient to represses IL4 transcription and can inhibit Th2-bias. This proposal aims to test the central hypothesis that Mina53 regulates Th2-bias and Th2-dependent disease, by investigating: (1) how Mina53 regulates IL4 expression; (2) how Mina53 gene expression is regulated; (3) what are the relative contributions to Th2-bias of Mina53 activity in progenitor T helper cells and dendritic cells?
Significance The global significance of this proposal arises from the critical role of TH2 bias in immune responses elicited by tolerogens, pathogens and allergens. Deeper mechanistic understanding of TH2 bias will provide new targets for diagnostic and therapeutic interventions in autoimmune, infectious and allergic diseases affecting the lives of millions of people.
| Pillai, Meenu R; Lian, Shangli; Bix, Mark (2014) Mina: a Th2 response regulator meets TGF?. Curr Opin Immunol 31:38-43 |
| Lian, Shangli; Potula, Hari Hara S K; Pillai, Meenu R et al. (2013) Transcriptional activation of Mina by Sp1/3 factors. PLoS One 8:e80638 |
| Okamoto, Mariko; Van Stry, Melanie; Chung, Linda et al. (2009) Mina, an Il4 repressor, controls T helper type 2 bias. Nat Immunol 10:872-9 |
