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A Regulatory Feedback between Plasmacytoid Dendritic Cells and Regulatory B Cells Is Aberrant in Systemic Lupus Erythematosus

Menon, M; Blair, PA; Isenberg, DA; Mauri, C; (2016) A Regulatory Feedback between Plasmacytoid Dendritic Cells and Regulatory B Cells Is Aberrant in Systemic Lupus Erythematosus. Immunity , 44 (3) pp. 683-697. 10.1016/j.immuni.2016.02.012. Green open access

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Abstract

Signals controlling the generation of regulatory B (Breg) cells remain ill-defined. Here we report an "auto"-regulatory feedback mechanism between plasmacytoid dendritic cells (pDCs) and Breg cells. In healthy individuals, pDCs drive the differentiation of CD19(+)CD24(hi)CD38(hi) (immature) B cells into IL-10-producing CD24(+)CD38(hi) Breg cells and plasmablasts, via the release of IFN-α and CD40 engagement. CD24(+)CD38(hi) Breg cells conversely restrained IFN-α production by pDCs via IL-10 release. In systemic lupus erythematosus (SLE), this cross-talk was compromised; pDCs promoted plasmablast differentiation but failed to induce Breg cells. This defect was recapitulated in healthy B cells upon exposure to a high concentration of IFN-α. Defective pDC-mediated expansion of CD24(+)CD38(hi) Breg cell numbers in SLE was associated with altered STAT1 and STAT3 activation. Both altered pDC-CD24(+)CD38(hi) Breg cell interactions and STAT1-STAT3 activation were normalized in SLE patients responding to rituximab. We propose that alteration in pDC-CD24(+)CD38(hi) Breg cell interaction contributes to the pathogenesis of SLE.

Type: Article
Title: A Regulatory Feedback between Plasmacytoid Dendritic Cells and Regulatory B Cells Is Aberrant in Systemic Lupus Erythematosus
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.immuni.2016.02.012
Publisher version: http://dx.doi.org/10.1016/j.immuni.2016.02.012
Language: English
Additional information: Copyright © 2016 The Authors This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). This document was posted here by permission of the publisher. At the time of the deposit, it included all changes made during peer review, copy editing, and publishing. The U. S. National Library of Medicine is responsible for all links within the document and for incorporating any publisher-supplied amendments or retractions issued subsequently. The published journal article, guaranteed to be such by Elsevier, is available for free, on ScienceDirect, at: http://dx.doi.org/10.1016/j.immuni.2016.02.012
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery.ucl.ac.uk/id/eprint/1501016
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