{"doi":"10.1002/art.41813","title":"Expansion of Fcγ Receptor <scp>IIIa</scp>–Positive Macrophages, Ficolin 1–Positive <scp>Monocyte‐Derived</scp> Dendritic Cells, and Plasmacytoid Dendritic Cells Associated With Severe Skin Disease in Systemic Sclerosis","abstract":"OBJECTIVE: In this study, we sought a comprehensive understanding of myeloid cell types driving fibrosis in diffuse cutaneous systemic sclerosis (dcSSc) skin. METHODS: We analyzed the transcriptomes of 2,465 myeloid cells from skin biopsy specimens from 12 dcSSc patients and 10 healthy control subjects using single-cell RNA sequencing. Monocyte-derived dendritic cells (mo-DCs) were assessed using immunohistochemical staining and immunofluorescence analyses targeting ficolin-1 (FCN-1). RESULTS: A t-distributed stochastic neighbor embedding analysis of single-cell transcriptome data revealed 12 myeloid cell clusters, 9 of which paralleled previously described healthy control macrophage/DC clusters, and 3 of which were dcSSc-specific myeloid cell clusters. One SSc-associated macrophage cluster, highly expressing Fcγ receptor IIIA, was suggested on pseudotime analysis to be derived from normal CCR1+ and MARCO+ macrophages. A second SSc-associated myeloid population highly expressed monocyte markers FCN-1, epiregulin, S100A8, and S100A9, but was closely related to type 2 conventional DCs on pseudotime analysis and identified as mo-DCs. Mo-DCs were associated with more severe skin disease. Proliferating macrophages and plasmacytoid DCs were detected almost exclusively in dcSSc skin, the latter clustering with B cells and apparently derived from lymphoid progenitors. CONCLUSION: Transcriptional signatures in these and other myeloid populations indicate innate immune system activation, possibly through Toll-like receptors and highly up-regulated chemokines. However, the appearance and activation of myeloid cells varies between patients, indicating potential differences in the underlying pathogenesis and/or temporal disease activity in dcSSc.","journal":"Arthritis & Rheumatology","year":2021,"id":151420,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":83,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9127,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":12145,"name":"Tracy Tabib","orcid":"0000-0003-4053-988X","position":1,"is_corresponding":false},{"id":496096,"name":"Christina Morse","orcid":"0000-0002-5744-0512","position":2,"is_corresponding":false},{"id":643951,"name":"Yi Yang","orcid":"0000-0001-9852-5988","position":3,"is_corresponding":false},{"id":332660,"name":"Robyn T. Domsic","orcid":"0000-0002-2765-0922","position":4,"is_corresponding":false},{"id":249352,"name":"Dinesh Khanna","orcid":"0000-0003-1412-4453","position":5,"is_corresponding":false},{"id":7274,"name":"Robert Lafyatis","orcid":"0000-0002-9398-5034","position":6,"is_corresponding":false},{"id":643950,"name":"Dan Xue","orcid":"0000-0002-0162-980X","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-18T23:43:16.823357Z","pmid":"34042322","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}