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• W4285992353 abstract "Type 1 interferons (IFN-1) are major drivers of disease activity in systemic (SLE) and cutaneous lupus erythematosus (CLE). Plasmacytoid dendritic cells (pDCs) are the major producers of IFN-1 during viral infection. pDCs are reduced in the circulation in SLE and have recently been shown to have an exhausted phenotype, suggesting that pathogenic pDCs were located in the end organs. We performed imaging mass cytometry of treatment naïve CLE skin (n=48), which revealed only 8.5% (IQR 0.0-22.22) of pDCs were IFNa+. Across all CLE biopsies, pDCs were the second lowest contributor of absolute IFNa+ cells (Median 1; IQR 0-4.5), with B lymphocytes being the smallest contributor. Classic dendritic cells (cDCs) and macrophages (Mf) were the largest relative and absolute contributors of IFNa in CLE. For IFNb, only 16.7% of pDCs were positive, compared to 60.7% of CD14+CD16+ Mf. pDCs were also the second lowest contributors of IFNb+ cells (Median 1; IQR 0-7), with B lymphocytes again being the lowest. We then performed mRNA in situ hybridization for CLEC4C (BDCA2) and IFN-1 (a, b, k) genes to confirm these findings. IFN-1 mRNA was detected in ITGAX (CD11c) positive cDCs but we did not identify colocalization of CLEC4C and IFN-1 mRNA. We then eluted leukocytes from CLE skin for flow cytometry. Flow cytometry showed a median of 5.2% of pDCs were positive for IFNa (IQR 3.8-9.6), compared with other myeloid cell lineages such as CD68+ Mf 35.9% (26.4-40.7), M1 Mf 23.7% (21.6-31.7), and M2 Mf 35.9% (26.4-40.7). We also performed CyTOF on CLE PBMCs with a 41-marker panel, including a pan-IFNa which demonstrated minimal staining of pDCs with IFN-1 compared to other myeloid cell lineages. Taken together, these findings suggest pDCs may not play the central role in CLE as major IFN-1 producers and myeloid cells are larger contributors of IFN-1 in numbers and as a percent. pDCs may have a pathogenic role in CLE through IFN-1-independent mechanisms." @default.
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• W4285992353 date "2022-08-01" @default.
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• W4285992353 title "066 Plasmacytoid dendritic cells are not major producers of type 1 interferons in cutaneous lupus" @default.
• W4285992353 doi "https://doi.org/10.1016/j.jid.2022.05.120" @default.
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