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

V Gies, JN Schickel, S Jung, A Joublin, S Glauzy… - JCI insight, 2018 - ncbi.nlm.nih.gov
V Gies, JN Schickel, S Jung, A Joublin, S Glauzy, AM Knapp, A Soley, V Poindron, A Guffroy…
JCI insight, 2018ncbi.nlm.nih.gov
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 …
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.
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