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

• Published in: Journal of investigative dermatology Vol. 144; no. 6; pp. 1262 - 1272.e7
• Main Authors: Vazquez, Thomas, Patel, Jay, Kodali, Nilesh, Diaz, DeAnna, Bashir, Muhammad M., Chin, Felix, Keyes, Emily, Sharma, Meena, Sprow, Grant, Grinnell, Madison, Dan, Joshua, Werth, Victoria P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2024
• Subjects: Adult; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dermatology; Female; Humans; IFN-α; Imaging mass cytometry; Immunology; Immunophenotyping; Interferon Type I - immunology; Interferon Type I - metabolism; Lupus Erythematosus, Cutaneous - immunology; Lupus Erythematosus, Cutaneous - pathology; Lupus Erythematosus, Discoid - immunology; Lupus Erythematosus, Discoid - pathology; Male; Middle Aged; Rheumatology; Skin - immunology; Skin - pathology; RT; cDC; Dermatology; Rheumatology; GZMB; IQR; SLE; pDC; SCLE; IFN-α; Immunology; CSB; Th; HC; DLE; CLASI; CLE; CyTOF; Imaging mass cytometry; IMC
• ISSN: 0022-202X; 1523-1747; 1523-1747
• DOI: 10.1016/j.jid.2023.10.039

The immunologic drivers of cutaneous lupus erythematosus (CLE) and its clinical subtypes remain poorly understood. We sought to characterize the immune landscape of discoid lupus erythematosus and subacute CLE using multiplexed immunophenotyping. We found no significant differences in immune cell percentages between discoid lupus erythematosus and subacute CLE (P > .05) with the exception of an increase in TBK1 in discoid lupus erythematosus (P < .05). Unbiased clustering grouped subjects into 2 major clusters without respect to clinical subtype. Subjects with a history of smoking had increased percentages of neutrophils, disease activity, and endothelial granzyme B compared with nonsmokers. Despite previous assumptions, plasmacytoid dendritic cells (pDCs) did not stain for IFN-1. Skin-eluted and circulating pDCs from subjects with CLE expressed significantly less IFNα than healthy control pDCs upon toll-like receptor 7 stimulation ex vivo (P < .0001). These data suggest that discoid lupus erythematosus and subacute CLE have similar immune microenvironments in a multiplexed investigation. Our aggregated analysis of CLE revealed that smoking may modulate disease activity in CLE through neutrophils and endothelial granzyme B. 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.