title: IFN-β therapy modulates B-cell and monocyte crosstalk via TLR7 in multiple sclerosis patients.
abstract: The implication of B lymphocytes in the immunopathology of multiple sclerosis (MS) is increasingly recognized. Here we investigated the response of B cells to IFN-β, a first-line therapy for relapsing-remitting MS patients, upon stimulation with TLR. IFN-β restored the frequency of TLR7-induced IgM and IgG-secreting cells in MS patients to the levels found in healthy donors, showing a specific deficiency in the TLR7 pathway. However, no difference was observed in the TLR9 response. Furthermore, in MS-derived PBMCs, TLR7-mediated production of IL-6 and the ex vivo expression of B-cell-activating factor of the TNF family, two crucial cytokines for B-cell differentiation and survival, were induced by IFN-β. Depletion of monocytes, which are key producers of both IL-6 and B-cell-activating factor of the TNF family, showed that TLR7-mediated B-cell differentiation into Ig-secreting cells is strongly dependent on the cross-talk between B cells and monocytes. Accordingly, impaired expression of TLR7 mRNA was observed in PBMCs and monocytes isolated from MS-affected individuals as compared with those from healthy donors, which was rescued by IFN-β therapy. Collectively, our data unveil a novel TLR7-regulated mechanism in in vivo IFN-β-stimulated whole leukocytes that could be exploited to define new TLR7-based strategies for the treatment of MS.
authors: Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
authors: Elena
authors: E
authors: Giacomini
authors: Martina
authors: M
authors: Severa
authors: Fabiana
authors: F
authors: Rizzo
authors: Rosella
authors: R
authors: Mechelli
authors: Viviana
authors: V
authors: Annibali
authors: Giovanni
authors: G
authors: Ristori
authors: Valeria
authors: V
authors: Riccieri
authors: Marco
authors: M
authors: Salvetti
authors: Eliana Marina
authors: EM
authors: Coccia
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020239:Receptor Cross-Talk / Q000187:drug effects* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051199:Toll-Like Receptor 7 / Q000276:immunology*
chemical_list: D007155:Immunologic Factors; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7; D016899:Interferon-beta
keywords: B cell; IFN-β; Monocyte; Multiple sclerosis; TLR