We sought a comprehensive understanding of myeloid cell types driving fibrosis in diffuse cutaneous systemic sclerosis (dcSSc) skin.
We analyzed the transcriptomes of 2,465 myeloid cells skin biopsies from 10 healthy controls (HCs) and 12 dcSSc patients by single-cell RNA-sequencing (scRNA-seq). Monocyte-derived dendritic cells were stained by immunohistochemistry and immunofluorescence targeting FCN1.
T-stochastic neighbor embedding analysis of single cell transcriptome data revealed 12 myeloid cell clusters, nine of which paralleled previously described HC Mφ/DC clusters and three of which were dcSSc-specific myeloid cell clusters. One SSc-associated macrophage cluster, highly expressing FCGR3A, on pseudotime analysis was suggested to derive from normal CCR1
Transcriptional signatures in these and other myeloid populations indicate innate immune activation, possibly through TLRs, and highly upregulated chemokines. However, the appearance and activation of myeloid cells is variable between patients, indicating differing underlying pathogenesis and/or temporal disease activity.