Objective: Tolerogenic dendritic cells (tolDCs) have emerged as a potential treatment for rheumatoid arthritis (RA). However, the detailed mechanism requires further investigation. In this study, we aimed to explore the effects of tolDCs on T-cell differentiation and NLRP3-mediated pyroptosis in a collagen-induced arthritis (CIA) rat model.
Methods: TolDCs were induced using NF-κB ODN decoy. The efficacy of tolDCs intervention in alleviating arthritis symptoms was evaluated in CIA rats. Flow cytometry was employed to analyze CD4+ T-cell subpopulations, while scanning electron microscopy was utilized to observe pyroptosis morphology. Immunohistochemistry was used to assess the expression of pyroptosis-associated proteins.
Results: TolDCs intervention significantly reduced joint inflammation and damage in CIA rats. Moreover, it successfully restored the balance of Th1/Th2 cells as well as the balance of Treg/Th17 cells. Furthermore, tolDCs intervention effectively suppressed NLRP3-mediated pyroptosis in the synovium, decreasing the release of IL-1β and IL-18.
Conclusion: Our findings underscore the efficacy of tolDCs in attenuating CIA progression through modulation of CD4+ T-cell subpopulations and inhibition of NLRP3-mediated pyroptosis.
Keywords: Collagen-induced arthritis; Pyroptosis; Rheumatoid arthritis; T-cell differentiation; Tolerogenic dendritic cells.
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