Exploring myeloid cell heterogeneity in autoimmune skin diseases with novel multiomics insights

Inflammatory skin disorders comprise a diverse set of conditions exhibiting unique characteristics. Our objective was to systematically compare the affected and unaffected skin of individuals with dermatomyositis (DM), cutaneous lupus (CLE), psoriasis, and vitiligo using a minimally invasive suction-blistering method combined with single-cell assays and Olink proteomics.

 

Single cell RNA sequencing data revealed a heterogeneous population of myeloid cells with disease-specific similarities and differences, including two different subtypes of Langerhans cells (both significantly diminished in lesional skin of psoriasis, CLE, and DM), as well as a unique population of tolerogenic-like myeloid cells that tend to increase in skin disease states with predominance in lupus and psoriasis.

 

In line with differences in cell type across skin diseases, Olink’s Proximity Extension Assay revealed disease-specific differences in cytokine levels, including high levels of IFNB1 in DM skin, IFNA2 in CLE, IL17 in psoriasis, and IFNG ,CXCL9 and CXCL10 in vitiligo. Type I interferons were shown to contribute to DM and CLE pathogenesis significantly. Our in vitro investigation further revealed that IFN-I significantly increased the expression of inflammatory chemoattractant CXCL9/10/11/13 while enhancing CD8 and CD4 cytotoxicity.

 

Overall, these results uncover disease-specific myeloid cells differentiating autoimmune skin disorders and spotlights specific cellular targets for IFN-I-mediated skin diseases.

 

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