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

Area of Science:

• Immunology
• Molecular Biology
• Autoimmune Diseases

Background:

• POU domain class 2-associating factor 1 (Bob1) is primarily expressed in B cells and regulates B cell homeostasis and humoral immunity.
• Bob1's function in T cell subsets like follicular helper T cells, Th1, and Th2 cells is established, but its role in other T cell subsets remained unclear.
• Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated autoimmune disease model.

Purpose of the Study:

• To investigate the role of Bob1 in T helper 17 (Th17) cell differentiation and function.
• To elucidate the molecular mechanism by which Bob1 influences Th17 cell activity.
• To determine Bob1's involvement in autoimmune diseases mediated by Th17 cells.

Main Methods:

• Utilized Bob1 knockout (KO) mice to study EAE susceptibility.
• Analyzed Th17 cell differentiation in Bob1 KO T cells.
• Investigated the interaction between Bob1 and RORγt using biochemical assays.
• Assessed IL-17A transcription activity and the formation of a DNA-Oct1-Bob1 ternary complex.

Main Results:

• Bob1 KO mice exhibited resistance to MOG35-55-induced EAE.
• Bob1 KO T cells showed defects in Th17 differentiation.
• Bob1 directly interacts with the ligand-binding domain of RORγt, enhancing IL-17A transcription.
• Bob1-mediated IL-17A induction requires the formation of a DNA-Oct1-Bob1 ternary complex.

Conclusions:

• Bob1 enhances IL-17A expression in Th17 cells both in vivo and in vitro through interaction with RORγt.
• Bob1 plays a critical role in Th17 cell differentiation and function.
• Bob1 is implicated as a pivotal factor in Th17-mediated autoimmune diseases like EAE.