Fu, YongyaoKoh, ByungheeKuwahara, MakotoUlrich, Benjamin J.Kharwadkar, RakshinYamashita, MasakatsuKaplan, Mark H.2021-08-022021-08-022020-10-01Fu, Y., Koh, B., Kuwahara, M., Ulrich, B. J., Kharwadkar, R., Yamashita, M., & Kaplan, M. H. (2019). BATF-Interacting Proteins Dictate Specificity in Th Subset Activity. The Journal of Immunology, 203(7), 1989–1998. https://doi.org/10.4049/jimmunol.19001280022-1767, 1550-6606https://hdl.handle.net/1805/26317The basic leucine zipper (bZIP) transcription factor BATF is expressed in multiple Th subsets and cooperates with other factors to regulate gene transcription. BATF activates lineage-specific cytokines in Th subsets, activating IL-9 in Th9 cells and IL-17 in Th17 cells, but not IL-9 or IL-17 in the reciprocal subset. The mechanism for this restricted activity is unclear. In this report we define BATF binding partners that contribute to Th subset-specific functions. Although BATF and IRF4 are expressed in greater amounts in Th9 than Th17, increased expression of both factors is not sufficient to induce IL-9 in Th17 cells. BATF also requires heterodimer formation with Jun family members to bind DNA and induce gene expression. Using primary mouse T cell culture, we observed that JunB and c-Jun, but not JunD, promote IL-9 production in Th9 cells. Ectopic expression of BATF with either JunB or c-Jun generates modest but significant increases in IL-9 production in Th17 cells, suggesting that the low expression of Jun family members is one factor limiting the ability of BATF to induce IL-9 in Th17 cells. We further identified that Bach2 positively regulates IL-9 production by directly binding to the Il9 gene and by increasing transcription factor expression in Th9 cells. Strikingly, co-transduction of Bach2 and BATF significantly induces IL-9 production in both Th9 and Th17 cells. Taken together, our results reveal that JunB, c-Jun and Bach2 cooperate with BATF toen-USGene Expression RegulationImmunologyInterferon Regulatory FactorsTh17 CellsArticle