Signaling pathways via BAFF receptor/Nav1.7 channel contribute to the activation of monocytes and B cells in patients with Sjögren’s disease 2254637

Abstract

Abstract Introduction We reported that the expression of a BAFF receptor, BR3, was enhanced in monocytes in patients with Sjögren’s disease (SjD), and that BAFF induced production of IL-6 by the cells. In addition, we found that IL-6 produced by BAFF-stimulated monocyte induced IgG production by co-cultured B cells. In our previous study, we also found that the inhibitors against Nav channel suppressed BAFF-induced IL-6 production by THP-1, a human monocytic leukemia cell line. Since the voltage gated sodium channel 1.7 (Nav1.7) was known to be involved in the production of IL-6 in monocytic lineage of patients of inflammatory diseases, we investigated the possible involvement of Nav1.7 in the BAFF signaling pathway in SjD monocytes. Methods The expression levels of BR3 and Nav1.7 in peripheral monocytes from patients with SjD (n = 108) and healthy controls (HC; n = 28) were analyzed by FACS. PBMCs were stimulated in vitro with a mixture of anti-IgM, anti-CD40, IL-21 and BAFF in the presence or absence of a specific inhibitor against Nav1.7. The amount of IgG produced by the cells was measured by ELISA. The expression level of Nav1.7 in the cells was analyzed by qPCR. Results The proportion of Nav1.7- and BR3-positive cells in monocytic population (Nav1.7+/CD14+, BR3+/CD14+) were significantly elevated in SjD as compared to HC. The Nav1.7+/CD14+ ratio was significantly correlated with BR3+/CD14+ ratio in SjD patients. Of note is that BAFF induced not only IL-6 production by SjD monocytes, but also the Nav1.7 expression in the cells. Moreover, a Nav1.7 specific inhibitor suppressed BAFF-induced IL-6 overproduction by SjD monocytes and elevated IgG production from stimulated PBMCs in a dose dependent manner. Conclusion These data and our previous data collectively suggest that Nav 1.7 signaling pathway is involved in the BAFF signaling pathway especially in IL-6 production by monocytes and IgG production by B cells in SjD. Funding Source n/a Topic Categories Cytokines and Chemokines and their Receptors (CCR)