Dysregulation of the gene signature of effector regulatory T cells in the early phase of systemic sclerosis.

Autor:	Kobayashi S; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo.; Department of Medicine and Rheumatology, Tokyo Metropolitan Geriatric Hospital., Nagafuchi Y; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo.; Department of Functional Genomics and Immunological Diseases, Graduate School of Medicine, The University of Tokyo., Okubo M; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo., Sugimori Y; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo., Hatano H; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo., Yamada S; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo., Nakano M; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo., Yoshida R; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo., Takeshima Y; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo., Ota M; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo.; Department of Functional Genomics and Immunological Diseases, Graduate School of Medicine, The University of Tokyo., Tsuchida Y; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo., Iwasaki Y; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo., Setoguchi K; Department of Rheumatology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo., Kubo K; Department of Medicine and Rheumatology, Tokyo Metropolitan Geriatric Hospital., Okamura T; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo.; Department of Functional Genomics and Immunological Diseases, Graduate School of Medicine, The University of Tokyo., Yamamoto K; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo.; Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Kanagawa, Yokohama, Japan., Shoda H; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo., Fujio K; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo.
Jazyk:	angličtina
Zdroj:	Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2022 Oct 06; Vol. 61 (10), pp. 4163-4174.
DOI:	10.1093/rheumatology/keac031
Abstrakt:	Objectives: We evaluated flow-cytometric and transcriptome features of peripheral blood immune cells from early-phase (disease duration <5 years) SSc in comparison with late-phase SSc. Methods: Fifty Japanese patients with SSc (12 early SSc cases and 38 late SSc cases) and 50 age- and sex-matched healthy controls were enrolled. A comparison of flow-cytometric subset proportions and RNA-sequencing of 24 peripheral blood immune cell subsets was performed. We evaluated differentially expressed genes (DEGs), characterized the co-expressed gene modules, and estimated the composition of subpopulations by deconvolution based on single-cell RNA-sequencing data. As a disease control, idiopathic inflammatory myositis (IIM) patients were also evaluated. Results: Analysing the data from early and late SSc, fraction II effector regulatory T cell (Fr. II eTreg) genes showed a remarkable differential gene expression, enriched for genes related to oxidative phosphorylation. Although the flow-cytometric proportion of Fr. II eTregs was not changed in early SSc, deconvolution indicated expansion of the activated subpopulation. Co-expressed gene modules of Fr. II eTregs demonstrated enrichment of the DEGs of early SSc and correlation with the proportion of the activated subpopulation. These results suggested that DEGs in Fr. II eTregs from patients with early SSc were closely associated with the increased proportion of the activated subpopulation. Similar dysregulation of Fr. II eTregs was also observed in data from patients with early IIM. Conclusions: RNA-seq of immune cells indicated the dysregulation of Fr. II eTregs in early SSc with increased proportion of the activated subpopulation. (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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