Zinc finger protein 24 enhances the pro-inflammatory activities of Tc17 cells and Tc17.1 cells in mouse collagen-induced arthritis.

Tc17 cells and Tc17.1 cells contribute synovial inflammation during the development of rheumatoid arthritis (RA). However, the modulatory mechanisms of synovial Tc17 cells and Tc17.1 cells remain elusive. In the current study, we performed transcriptome profiling analysis on sorted live synovial Tc17 cells and Tc17.1 cells from a mouse model of collagen-induced arthritis (CIA). We found an array of differentially expressed genes (DEGs), which might be involved in the metabolism, cytokine signaling, and other biological aspects in synovial Tc17 and Tc17.1 cells. Importantly, we identified zinc finger protein 24 (ZNF24), a transcription factor, among the DEGs. ZNF24 knockdown impaired Tc17 differentiation and function in vitro, as evidenced by lower expression of IL-17A, RORγt, GM-CSF, IL-22, perforin, and granzyme B. ZNF24 knockdown resulted in similar effects on Tc17.1 differentiation and function in vitro. Furthermore, ZNF24 knockdown weakened the effects of Tc17 cells and Tc17.1 cells on inducing pro-inflammatory mediator expression in synovial fibroblasts. Adoptive transfer of Tc17.1 cells significantly exacerbated CIA development, whereas ZNF24-knockdown ameliorated the detrimental effect of Tc17.1 cells. Synovial fibroblasts up-regulated ZNF24 expression in Tc17 and Tc17.1 cells in a direct contact manner. The expression pattern and effect of ZNF24 were also observed in patients with RA and human Tc17 cells and Tc17.1 cells. Taken together, our study suggests that ZNF24 is a positive regulatory factor for Tc17 and Tc17.1 cells to exert pro-inflammatory effects in RA. We thus unveiled a novel mechanism by which the functions of synovial Tc17 cells and Tc17.1 cells are modulated.