Bob1 enhances RORγt-mediated IL-17A expression in Th17 cells through interaction with RORγt

POU domain class 2-associating factor 1 (also called Bob1), which is mainly expressed in B cells, regulates B cell homeostasis and controls humoral immune responses. Although Bobl is known to function reliably in T cell subsets including follicular helper T cells, Th1 cells and Th2 cells, it is unknown whether Bobl functions in other T cell subsets. In this study, we found that Bobl knock out (1(0) mice are resistant to experimental autoimmune encephalomyelitis (EAE) induced by MOG(35-55) peptide and that Bobl KO T cells are defective in Th17 differentiation. Importantly, Bobl interacts with retinoid acid receptor-related orphan receptor (ROR) gamma t (ROR gamma t), a signature transcription factor for Th17 cells, through the ligand-binding domain of ROR gamma t, thereby enhancing IL-17A transcription activity. IL-17A induction by Bobl requires the ability for its formation of a DNA-Oct1-Bob1 ternary complex. Thus, our findings demonstrate that Bobl enhances IL-17A expression in vivo and in vitro by interacting with ROR gamma t in Th17 cells, suggesting that Bobl plays a pivotal role in Th17-mediated autoimmune disease. (C) 2019 Elsevier Inc. All rights reserved.