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

Abstract

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 Bob1 is known to function reliably in T cell subsets including follicular helper T cells, Th1 cells and Th2 cells, it is unknown whether Bob1 functions in other T cell subsets. In this study, we found that Bob1 knock out (KO) mice are resistant to experimental autoimmune encephalomyelitis (EAE) induced by MOG35-55 peptide and that Bob1 KO T cells are defective in Th17 differentiation. Importantly, Bob1 interacts with retinoid acid receptor-related orphan receptor (ROR) gamma t (RORγt), a signature transcription factor for Th17 cells, through the ligand-binding domain of RORγt, thereby enhancing IL-17A transcription activity. IL-17A induction by Bob1 requires the ability for its formation of a DNA-Oct1-Bobl ternary complex. Thus, our findings demonstrate that Bob1 enhances IL-17A expression in vivo and in vitro by interacting with RORγt in Th17 cells, suggesting that Bob1 plays a pivotal role in Th17-mediated autoimmune disease.

• Authors: Ippei Ikegami, Hiromi Takaki, Shiori Kamiya, Ryuta Kamekura, Shingo Ichimiya
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 514 Issue 4 Pg. 1167-1171 (07 05 2019) ISSN: 1090-2104 [Electronic] United States
• PMID: 31103264 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Il17a protein, mouse
• Interleukin-17
• Nuclear Receptor Subfamily 1, Group F, Member 3
• Pou2af1 protein, mouse
• Trans-Activators

Topics

• Animals
• Female
• Interleukin-17 (biosynthesis, metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Nuclear Receptor Subfamily 1, Group F, Member 3 (metabolism)
• Th17 Cells (metabolism)
• Trans-Activators (deficiency, metabolism)