The role of berberine, a clinically relevant plant-derived alkaloid, in T-cell mediated immunosuppression

Abstract

Abstract Preliminary 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 arthritis induction in a collagen induced arthritis (CIA) mouse model, a common murine model for rheumatoid arthritis. As the interaction between Tfh cells and B cells is crucial for thymus-dependent humoral responses, this raises concern that the prolonged use of berberine could suppress the generation of such responses. In our current research we explored the effects of BBR in vitro on the differentiation of Tfh cells from naïve CD4+T cells (>95% pure) by examining the expression of the key Tfh cell surface molecules CXCR5, ICOS, and PD1 following BBR treatment. Such molecules are crucial for Tfh cell effector function. The treatment of BBR at 0.25 mg/mL, 0.50 μg/mL, and 1 mg/mL significantly reduced the expression of both CXCR5 (p <0.01) and ICOS (p < 0.01), but not PD1. It is important to note that in preliminary dose-response experiments, 0.50 mg/mL was the highest dose of BBR that did not significantly lead to cell death, indicating that the decreased expression of CXCR5 and ICOS at 0.25 mg/mL and 0.50 mg/mL are likely not due to cytotoxic effects. In the future, we plan to elucidate the mechanism by which BBR inhibits the expression of CXCR5 and ICOS by examining key cell signaling pathways that lead to Tfh activation and differentiation, and ultimately to CXCR5 and ICOS expression, following BBR treatment.