Mechanistic study of IL-17 inhibitors in alleviating inflammation in ankylosing spondylitis by regulating Treg cell function through modulation of the Ahr signaling pathway.

This study explored whether Interleukin-17 (IL-17) inhibitors alleviate inflammation in ankylosing spondylitis (AS) by modulating the aryl hydrocarbon receptor (Ahr) signaling pathway to influence regulatory T cell (Treg) function. A proteoglycan (PG)-induced mouse model of AS, comprising a control group, a model group (PG), and an IL-17 inhibitor treatment group (PG + Secukinumab), was established. Arthritis severity was assessed using arthritis scoring, histopathological analysis, molecular biology techniques, and flow cytometry to evaluate inflammation, expression of inflammatory factors, Ahr signaling pathway activity, and the proportion of Tregs. An Ahr inhibitor (CH-223191) was used in combination with secukinumab to validate the mechanism. The results showed that the IL-17 inhibitor significantly reduced arthritis inflammation in AS mice, downregulating the expression of pro-inflammatory factors such as IL-17, IL-6, and TNF-α. Moreover, it activated the Ahr signaling pathway while increasing the proportion of Tregs and the expression of their functional anti-inflammatory factors IL-10 and TGF-β. Administration of the Ahr inhibitor reversed the protective effects of the IL-17 inhibitor. In conclusion, the IL-17 inhibitor alleviated AS inflammation by activating the Ahr signaling pathway and enhancing Treg cell function, thus correcting immune imbalance. This study reveals a novel "IL-17 inhibitor-Ahr-Treg" immune regulatory axis, providing novel insights into immunotherapy for AS.