Cyclodextrin Inhibits Caveolin-1 to Regulate CD4+ T Cell Subset Differentiation and Ameliorate Rheumatoid Arthritis Progression.

OBJECTIVE: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by dynamically recurring inflammatory episodes, and targeting T cells has been shown to effectively alleviate RA. Caveolin-1 (CAV-1) is widely distributed in the membrane structures of immune cells and participates in the differentiation and homeostasis of CD4+ T cell subsets through signal transduction; however, its role in RA has not yet been investigated. This study aimed to examine the expression pattern and clinical relevance of CAV-1 in RA, and to elucidate its regulatory role in CD4+ T cell-mediated immune imbalance during disease progression. METHODS: This retrospective clinical study was conducted to detect serum CAV-1 levels in RA and healthy controls (HCs), characterize its expression in peripheral blood CD4+ T cells and synovial tissues, and evaluate its association with clinical parameters. A collagen-induced arthritis (CIA) mouse model was established and treated with the CAV-1 inhibitor hydroxypropyl-β-cyclodextrin (HP-β-CD). Joint pathology, CD4+ T cell infiltration, differentiation, and the expression of related inflammatory cytokines were assessed using histopathological and immunological approaches. RESULTS: CAV-1 expression in serum, CD4+ T cells, and synovial tissues was significantly higher in RA than in HC and was positively correlated with anti-cyclic citrullinated peptide antibody (Anti-CCP) and rheumatoid factor (RF) levels. HP-β-CD treatment markedly relieved joint inflammation and structural damage in CIA mice, reduced CD4+ T cell infiltration, and significantly suppressed the differentiation of T helper 1, T helper 17, and regulatory T (Treg) cells, accompanied by decreased expression of IFN-γ, IL-17A, and transforming growth factor-β (TGF-β). CONCLUSION: CAV-1 is aberrantly upregulated in RA and contributes to disease pathogenesis by regulating CD4+ T cell differentiation. Targeting CAV-1 may represent a promising strategy for RA diagnosis and immunomodulatory therapy.