Ginsenoside compound K decreases presentation of citrullinated peptides by regulating autophagy-induced autoantigen activation

Objective: Citrullinated vimentin (cVIM) triggers the immune response and is the primary autoantigen of rheumatoid arthritis (RA). Ginsenoside compound K (CK), which exerts significant anti-inflammatory effects, was the objective of this study. We aimed to investigate the role and mechanism of CK in regulating presentation of citrullinated peptides.

Methods: In RA fibroblast-like synoviocytes (RA-FLS), the expression of autoantigen cVIM, antigen presentation-related molecules, autophagy-related proteins, and autophagic flux were investigated. The effect of CK on the antigen presentation capability of FLS was also examined under conditions of autophagy induction and inhibition. Finally, Wistar rats were immunized with cVIM to evaluate the therapeutic effect of CK in an RA model.

Results: In RA-FLS, CK mitigated the expression of cVIM, autophagy-associated proteins, and antigen presentation-related molecules. This regulatory effect was associated with autophagy. cVIM-immunized rats exhibited more severe arthritis and higher levels of anti-CCP antibodies than those with adjuvant- and vimentin (VIM)-induced arthritis. CK significantly alleviated arthritis inflammation in cVIM-immunized rats.

Conclusions: CK alleviates cVIM-induced arthritis symptoms, with the regulation of autophagy presenting a key cellular event involved in cVIM generation and RA-FLS antigen-presenting ability.