Format

Send to

Choose Destination
See comment in PubMed Commons below
Eur J Immunol. 2013 Jul;43(7):1963-72. doi: 10.1002/eji.201243212. Epub 2013 May 28.

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

Author information

  • 1Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.

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.

© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

KEYWORDS:

B cell; IFN-β; Monocyte; Multiple sclerosis; TLR

[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley
    Loading ...
    Write to the Help Desk