Figure 2. Depletion of plasmacytoid dendritic cells by CSL362 potently and specifically inhibits TLR7- and TLR9-induced IFN-α production and IFN-α-inducible gene expression.

(A) IFN-α production, as measured by ELISA, in response to TLR4, TLR7, and TLR9 stimulation following CSL362 or isotype control pretreatment of healthy and SLE donor (n = 3 each) peripheral blood mononuclear cells (PBMCs). (B) Expression of 11 IFN-inducible genes (IFI44L, IFIT1, IFIT3, IRF7, ISG15, MX1, MX2, OAS1, OAS2, SERPING1, and XAF1), as determined by qPCR, in response to TLR1–9 agonist stimulation following CSL362 or isotype control pretreatment in healthy donor PBMCs (n = 4). (C) IFN-α production, as determined by ELISA, from healthy (n = 2) and SLE (n = 2) donor PBMCs that were depleted either of plasmacytoid dendritic cells (pDCs) or basophils and stimulated with TLR7 (imiquimod) or TLR9 (CpG C) agonist. Data are expressed as mean ± SEM, *P < 0.05 (Mann Whitney test).