IFN‐β therapy modulates B‐cell and monocyte crosstalk via TLR7 in multiple sclerosis patients

作者: Elena Giacomini , Martina Severa , Fabiana Rizzo , Rosella Mechelli , Viviana Annibali

DOI: 10.1002/EJI.201243212

关键词: Peripheral blood mononuclear cellTLR7MonocyteTLR9B cellBiologyMultiple sclerosisImmunologyEx vivoIn vivo

摘要: The implication of B lymphocytes in the immunopathology multiple sclerosis (MS) is increasingly recognized. Here we investigated response cells to IFN-β, a first-line therapy for relapsing-remitting MS patients, upon stimulation with TLR. IFN-β restored frequency TLR7-induced IgM and IgG-secreting patients levels found healthy donors, showing specific deficiency TLR7 pathway. However, no difference was observed TLR9 response. Furthermore, MS-derived PBMCs, TLR7-mediated production IL-6 ex vivo expression B-cell-activating factor TNF family, two crucial cytokines B-cell differentiation survival, were induced by IFN-β. Depletion monocytes, which are key producers both showed that into Ig-secreting strongly dependent on cross-talk between monocytes. Accordingly, impaired mRNA PBMCs monocytes isolated from MS-affected individuals as compared those rescued therapy. Collectively, our data unveil novel TLR7-regulated mechanism IFN-β-stimulated whole leukocytes could be exploited define new TLR7-based strategies treatment MS.

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