کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3063827 | 1580377 | 2016 | 8 صفحه PDF | دانلود رایگان |

• B cells from RRMS patients exhibit decreased IFNβ secretion and signaling.
• TLR7/TLR9 stimulation with exogenous IFNβ reconstitutes endogenous IFNβ expression.
• This combination therapy induces secretion of immunoregulatory cytokines in B cells.
• TLR7/9 agonists with IFNβ inhibit CD4+ cells' secretion of inflammatory cytokines.
• TLR7/9 agonists may enhance IFNβ's therapeutic effect in patients with RRMS.
We report that B cells from patients with RRMS have decreased endogenous IFN-β 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-β may effectively reconstitute endogenous IFN-β production deficit and induce the secretion of immunoregulatory cytokines by B cells. Both LOX/IFN-β and CpG/IFN-β in-vitro treatments of B cells from RRMS patients induced higher endogenous IFN-β gene expression in comparison to the exogenous IFN-β alone. CpG/IFN-β combination induced higher secretion of IL-10, TGF-β, and IL-27 in comparison to stimulation with IFN-β. Our study provides a basis for future clinical studies employing IFN-β and TLR7/9 agonists, which may enhance the resolution of the inflammatory response in RRMS.
Journal: Journal of Neuroimmunology - Volume 298, 15 September 2016, Pages 181–188