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Impaired TLR9 responses in B cells from patients with systemic lupus erythematosus
Vincent Gies, … , Eric Meffre, Anne-Sophie Korganow
Vincent Gies, … , Eric Meffre, Anne-Sophie Korganow
Published March 8, 2018
Citation Information: JCI Insight. 2018;3(5):e96795. https://doi.org/10.1172/jci.insight.96795.
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Research Article Immunology

Impaired TLR9 responses in B cells from patients with systemic lupus erythematosus

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Abstract

B cells play a central role in systemic lupus erythematosus (SLE) pathophysiology but dysregulated pathways leading to a break in B cell tolerance remain unclear. Since Toll-like receptor 9 (TLR9) favors the elimination of autoreactive B cells in the periphery, we assessed TLR9 function in SLE by analyzing the responses of B cells and plasmacytoid dendritic cells (pDCs) isolated from healthy donors and patients after stimulation with CpG, a TLR9 agonist. We found that SLE B cells from patients without hydroxychloroquine treatment displayed defective in vitro TLR9 responses, as illustrated by the impaired upregulation of B cell activation molecules and the diminished production of various cytokines including antiinflammatory IL-10. In agreement with CD19 controlling TLR9 responses in B cells, decreased expression of the CD19/CD21 complex on SLE B cells was detected as early as the transitional B cell stage. In contrast, TLR7 function was preserved in SLE B cells, whereas pDCs from SLE patients properly responded to TLR9 stimulation, thereby revealing that impaired TLR9 function in SLE was restricted to B cells. We conclude that abnormal CD19 expression and TLR9 tolerogenic function in SLE B cells may contribute to the break of B cell tolerance in these patients.

Authors

Vincent Gies, Jean-Nicolas Schickel, Sophie Jung, Aurélie Joublin, Salomé Glauzy, Anne-Marie Knapp, Anne Soley, Vincent Poindron, Aurélien Guffroy, Jin-Young Choi, Jacques-Eric Gottenberg, Jennifer H. Anolik, Thierry Martin, Pauline Soulas-Sprauel, Eric Meffre, Anne-Sophie Korganow

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Figure 1

Decreased CD19 and CD21 expression on SLE B cells.

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Decreased CD19 and CD21 expression on SLE B cells.
(A) CD19, CD21, CD81,...
(A) CD19, CD21, CD81, and CD225 mean fluorescence intensity (MFI) ratios of CD19+ B cells from quiescent (n = 22) and active (n = 10) systemic lupus erythematosus (SLE) patients compared with healthy donors (HDs; n = 39). (B) CD19 and CD21 MFI ratios of transitional, mature naive B cells from quiescent (n = 20) and active (n = 10) SLE patients compared with HDs (n = 37). The MFI ratio was determined as follows: (MFI of the considered marker)/(mean of the MFI of the considered marker in the HD group). *P < 0.05, **P < 0.005, ***P < 0.001 by 2-tailed Mann-Whitney U test.

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