Cd97 Alleviates Rheumatoid Arthritis By Inhibiting M1 Macrophage Polarization

This study aimed to uncover the function and underlying mechanism of CD97 in the development of rheumatoid arthritis (RA). Single-cell RNA sequencing data from synovium of RA patients was used to assess the expression of CD97 on macrophages. Adjuvant-induced arthritis (AIA) model was applied to induce RA in Cd97fl/fl mice and Lysm-Cre; Cd97CKO (Cd97CKO) mice. To explore the role of CD97 in ankle joints and tempotomandibular joints, we performed HE, safranin O/fast green, toluidine blue, and immunofluorescence staining. Moreover, shRNA was used to investigate the effect of CD97 on macrophage polarization. Bulk RNA sequencing and western blotting were conducted to elucidate the mechanisms of CD97 in regulating macrophage polarization. To validate the therapeutic effects of CD97 on rheumatoid arthritis, adeno-associated virus was injected into the ankle and temporomandibular joint cavities of AIA mice. Micro-CT and HE, safranin O/fast green, toluidine blue, and immunofluorescence staining were used to observe the synovial inflammation and bone destruction. CD97 was highly expressed in synovial macrophage subpopulations of RA patients and AIA mice. Cd97 deficiency exacerbated arthritis progression and promoted M1 macrophage polarization through PI3K/AKT/P38 signaling pathway. Additionally, intra-articular overexpression of Cd97 alleviated synovium inflammation of ankle joints and temporomandibular joints. This work elucidates that CD97 alleviates the progression of RA by regulating synovial macrophage polarization via PI3K/AKT/P38 pathway, thereby giving insights into potential treatment strategies for RA.