Abstract
Interleukin (IL)-21 is a major lineage-defining factor that promotes Tfh cell differentiation. The current study investigated the molecular basis of myricetin, a flavonoid that impedes IL-21-mediated differentiation of Tfh cells in RA. Through high-throughput virtual screening of natural compounds that inhibit IL-21, we found that myricetin binds to IL-21 and hampers its interaction with IL-21 receptor (IL-21R). Our in vivo studies demonstrated that myricetin treatment ameliorated the clinical manifestations in adjuvant-induced arthritis (AIA) mice by reducing paw thickness and cellular infiltration. In addition, myricetin inhibited splenic Tfh cell differentiation and IL-21 production in AIA mice. Myricetin negatively regulates JAK/STAT signaling and the downstream Bcl-6 transcription factor at the molecular level, which arrests Tfh cell differentiation. Our current research proposal to target IL-21 with myricetin inevitably represents a new molecular approach that expedites new alternative drugs for rheumatoid arthritis therapy.
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The data generated during the current study will be available from corresponding author on reasonable request.
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All experimental protocols were approved by the Institutional Animal Ethical Committee (IEAC) (vide registration no: VIT/IAEC/20/DEC2021/15) and were carried out in accordance with the norms put forth by the Committee for the Purpose of Control and Supervision on Experiments on Animals (CPCSEA), India.
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Jose, A.M., Samarpita, S., Panchal, N.K. et al. Selective blockade of IL-21 by myricetin impedes T follicular helper cell differentiation by negatively regulating the JAK/STAT/Bcl-6 pathway in a rheumatoid arthritis animal model. 3 Biotech 14, 25 (2024). https://doi.org/10.1007/s13205-023-03880-w
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DOI: https://doi.org/10.1007/s13205-023-03880-w