Abstract 24 — Myricetin Impedes Tfh Cell Differentiation and Ameliorates the Tumorigenic Phenotype of Adjuvant-Induced Arthritis FLS in Rheumatoid Arthritis

Background Rheumatoid arthritis (RA) is an autoimmune disorder characterized by destructive polyarthritis and extra-articular manifestations. Myricetin, a flavonoid, possesses several pharmacological benefits, including anti-arthritic effects. However, the specific role and molecular basis of myricetin in IL-21 mediated T follicular helper (Tfh) cell differentiation and activation of fibroblast-like synoviocytes (FLS) in RA remain unknown. In the present study, we decoded the therapeutic intervention of myricetin as an anti-arthritic small-molecule drug for impeding Tfh cell differentiation and for abrogating the RA-FLS-transformed aggressive phenotype. Methods In vivo experiments were conducted using an adjuvant-induced arthritis animal model to evaluate the effects of myricetin on Tfh cell differentiation, IL-21 production, choline kinase (ChoK) activation, and the JAK/STAT signaling pathway. Results In this study, myricetin was found to significantly inhibit the interaction between IL-21 and IL-21R, and at the molecular level, it suppressed JAK/STAT signaling and the downstream transcription factor Bcl-6, which decreased Tfh cell differentiation. Additionally, myricetin suppressed the IL-21-induced hyperproliferation of AIA-FLSs by downregulating the ChoK signaling cascade (Ras, Ral-GDS, and PI3K). Myricetin treatment reduced ChoK enzymatic activity and the proliferative, migratory, and invasive properties of AIA-FLS. Conclusion Taken together, our results demonstrated that myricetin is a promising therapeutic compound that abates IL-21-induced Tfh cell differentiation and the invasive behavior of AIA-FLS.