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• W4285606007 endingPage "154343" @default.
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• W4285606007 abstract "Our previous research revealed a novel function of berberine (BBR), a clinically relevant plant-derived alkaloid, as a suppressor of follicular T helper (Tfh) cell proliferation in secondary lymphoid organs of BBR-treated mice that underwent immunization for collagen-induced arthritis (CIA) in DBA1/J mice. Due to the importance of Tfh cell and B cell interactions in the generation of T cell-dependent humoral responses, the suppression of Tfh cell activity may have implications for the general safety of BBR as a prophylactic dietary supplement, and its potential use in antibody-driven autoimmune and hypersensitivity disorders. This research aims to characterize BBR's impact on the activation, differentiation, and proliferation of Tfh cells by examining the expression of key extracellular signaling molecules, as well as the activity of intracellular signaling molecules involved in the Ca2+-calcineurin-NFAT pathway and STAT3 phosphorylation, following activation. In vitro experimental study using primary tissues. To explore the direct effects of BBR on the proliferation and differentiation of Tfh cells, isolated naïve CD4+ T cells (>95% pure) were activated and differentiated into pre- Tfh cells in the presence or absence of BBR. The resulting Tfh cell populations and the expression of the key extracellular molecules CXCR5, ICOS, and PD-1 were measured. In addition, we examined the impact of BBR treatment on the activity of key intracellular signaling molecules involved in Tfh cell activation and differentiation following TCR ligation and/or CD28 signaling (p-ZAP-70, p-Lck, p-PLCγ1, NFATc1 and intracellular calcium, Ca2+, concentrations), as well as IL-6 signaling (p-STAT3). Treatment with BBR significantly reduced the expression of both CXCR5 (p < 0.01) and ICOS (p < 0.005), but not PD-1, and reduced the percentage of Tfh cells within the total CD4+ T cell population. BBR treatment also led to a reduction in intracellular Ca2+ flux, activation of p-STAT3, and IL-21 production. Our observations provide insight into the mechanism of BBR-mediated Tfh cell suppression and suggest that BBR treatment can directly inhibit Tfh cell activity, perhaps through interfering with cytokine receptor or downstream signaling." @default.
• W4285606007 created "2022-07-16" @default.
• W4285606007 creator A5027613847 @default.
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• W4285606007 date "2022-10-01" @default.
• W4285606007 modified "2023-10-11" @default.
• W4285606007 title "Exploring the mechanism of berberine-mediated Tfh cell immunosuppression" @default.
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• W4285606007 doi "https://doi.org/10.1016/j.phymed.2022.154343" @default.
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