19th International Congress of Immunology - IUIS 2025

Recent data suggest that vitamin K2 (VK2) supplementation has beneficial effects on inflammatory diseases, including rheumatoid arthritis (RA). However, the underlying mechanisms are poorly understood. In this study, the effects of VK2 and its potential anti-inflammatory/immunomodulatory properties were investigated in a rat model of RA, collagen-induced arthritis (CIA). Female Dark Agouti rats were immunized with bovine type II collagen (CII) in incomplete Freund`s adjuvant to induce CIA. Treatment with VK2 (MK-7) (50 mg/kg/day/orally) began one day prior to immunization and continued until the day of sacrifice. The clinical picture was determined by clinical scoring and histological analysis. The phenotypic and functional characteristics of lymphoid organ (LO) cells, including splenocytes and draining lymph node (dLN) cells, were analyzed by flow cytometry. Cytokine concentrations in hind paw tissue culture supernatants and levels of CII-specific IgG antibodies in serum were measured by ELISA. VK2 reduced the arthritic score and the severity of ankle joint inflammation in CIA rats. This was accompanied by a shift in the balance between proinflammatory (TNF-a and IL-6) and anti-inflammatory (IL-10) cytokines towards later in the paws of treated rats. CD11b+ cells in LOs of treated rats exhibited decreased production of TNF-a and IL-1b and decreased expression of CD86 (in dLNs and spleen) and MHC II and TLR4 (in spleen), suggesting a less inflammatory phenotype. Additionally, the frequencies of CD4+ cells producing IL-17 and IFN-g were lower in the dLNs, while regulatory CD4+FoxP3+ cell frequency was higher in the treated rats. Lower serum levels of CII-specific antibodies corresponded with a lower frequency of CD45RA+ cells (B cells) in the LOs of treated rats. These results suggest that preventive VK2 treatment improves the clinical presentation of RA in rat CIA model. Furthermore, they highlight potential mechanisms underlying its anti-inflammatory/immunoregulatory effect.