BATF dependency of Th9-associated genes (HYP7P.290)

Abstract

Abstract Th9 cells are a recently described T helper subset that develops in the presence of TGF-β and IL-4. Th9 cells promote allergic inflammation, anti-tumor immunity, and may contribute to the regulation of auto inflammatory disease. Th9 cells are specialized for IL-9 production and this requires transcription factors including STAT6, PU.1 and IRF4. We have recently described that BATF promotes Th9 development in both mouse and human cells and BATF is required for T cells to promote the development of allergic inflammation. BATF-transduced Th9 cells demonstrated a potent ability to promote allergic inflammation in vivo compared to control transduced Th9 cells. To begin to define the transcriptional network controlling genes in Th9 cells, we characterized the dependence of Th9-enriched genes on each transcription factor, including BATF. Multiple genes including transcription factors, cytokines, and cytokine receptors were BATF-dependent. Unique functional properties of Th9 cells are suggested by the Th9-enriched expression of IL-33R, IL-25R, granzyme A, ephrin A5, and the salt-sensitive serum glucocorticoid kinase. BATF is required for 14/19 genes studied in detail thus far, suggesting that it is a major controller of the Th9 genetic program. Further defining of the module of BATF-dependent genes will aid in integrating the circuitry of Th9 development and function.