The Kaplan Lab identified an unexpected role for STAT3 in Th2 and now further explores how the STAT3 signal is integrated in various Th subsets. They identified several interesting aspects of STAT3 signaling in Th2 cells including a balance with activation of other STAT proteins, and the induction of genes that may identify a novel functional subset of Th cells.
This latter point links to another interest of the laboratory, allergic skin inflammation. Over a decade ago the lab developed a mouse model transgenic for a constitutively active STAT6 in T cells. These mice are predisposed towards spontaneous allergic inflammation, particularly in the skin. The lab has characterized the pathogenesis of skin inflammation in this strain focusing in two areas. The first uses this mouse model to test the interactions between the hyperactive Th2 immune response and dysfunction in the barrier function of the skin. The second approach in this area is to define how Th2 cytokines, specifically IL-4, impact keratinocyte gene expression and differentiation. We are using RNA-seq and ChIP-seq approaches to define how the IL-4/STAT6 pathway function in non-immune cells.