Plasmacytoid Dendritic Cells Are Not Major Producers of Type 1 IFN in Cutaneous Lupus: An In-Depth Immunoprofile of Subacute and Discoid Lupus

Abstract

The immunologic drivers of cutaneous lupus erythematosus (CLE) and its clinical subtypes remains poorly understood. We sought to characterize the immune landscape of discoid lupus erythematosus (DLE) and subacute CLE (SCLE) using multiplexed immunophenotyping. We found no significant differences in immune cell percentages between DLE and SCLE (p>0.05) with the exception of an increase in TANK binding kinase 1 (TBK1) in DLE (p<0.05). Unbiased clustering grouped subjects into two major clusters without respect to clinical subtype. Subjects with a history of smoking had increased percentages of neutrophils, disease activity, and endothelial granzyme B than non-smokers. Despite previous assumptions, plasmacytoid dendritic cells (pDCs) did not stain for type 1 interferon (IFN-1). Skin-eluted and circulating pDCs from CLE subjects expressed significantly less IFNα than healthy control pDCs upon toll like receptor (TLR) 7 stimulation ex vivo (p<0.0001). These data suggest that DLE and SCLE have similar immune microenvironments in a multiplexed investigation. Our aggregated analysis of CLE revealed that smoking may modulate disease activity in CLE via neutrophils and endothelial GZMB. Notably, our data suggest that pDCs are not the major producers of IFN-1 in CLE. Future in vitro studies to investigate the role of pDCs in CLE are needed.