Toll-like receptor (TLR)7 and TLR9 agonists enhance interferon (IFN) beta-1a's immunoregulatory effects on B cells in patients with relapsing-remitting multiple sclerosis (RRMS)

作者：Tao Yazhong; Zhang Xin; Markovic Plese Silva^*

来源：Journal of Neuroimmunology, 2016, 298: 181-188.

DOI：10.1016/j.jneuroim.2016.07.019

• Multiple sclerosis
• IFN-beta-1a
• TLR7
• TLR9
• B cells

We report that B cells from patients with RRMS have decreased endogenous IFN-beta secretion and deficient IFN receptor (IFNAR)1/2 and TLR7 gene expression in comparison to healthy controls (HCs), which may contribute to disregulation of cytokine secretion by B cells. We propose that TLR7 and TLR9 stimulation with loxorubin (LOX) and CpG, in combination with exogenous IFN-beta may effectively reconstitute endogenous IFN-beta production deficit and induce the secretion of immunoregulatory cytokines by B cells. Both LOX/IFN-beta and CpG/IFN-beta in-vitro treatments of B cells from RRMS patients induced higher endogenous IFN-beta gene expression in comparison to the exogenous IFN-beta alone. CpG/IFN-beta combination induced higher secretion of IL-10, TGF-beta, and IL-27 in comparison to stimulation with IFN-beta. Our study provides a basis for future clinical studies employing IFN-beta and TLR7/9 agonists, which may enhance the resolution of the inflammatory response in RRMS.

• 出版日期2016-9-15