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Tytuł:
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A Novel Type I Interferon Primed Dendritic Cell Subpopulation in TREX1 Mutant Chilblain Lupus Patients.
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Autorzy:
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Eugster A; Center for Regenerative Therapies Dresden, Faculty of Medicine Technische Universität (TU), Dresden, Germany.
Müller D; Center for Regenerative Therapies Dresden, Faculty of Medicine Technische Universität (TU), Dresden, Germany.
Gompf A; Center for Regenerative Therapies Dresden, Faculty of Medicine Technische Universität (TU), Dresden, Germany.
Reinhardt S; Center for Molecular and Cellular Bioengineering (CMCB), DRESDEN-Concept Genome Center Technische Universität, Dresden, Germany.
Lindner A; Center for Regenerative Therapies Dresden, Faculty of Medicine Technische Universität (TU), Dresden, Germany.
Ashton M; Center for Regenerative Therapies Dresden, Faculty of Medicine Technische Universität (TU), Dresden, Germany.
Zimmermann N; Faculty of Medicine, Paul Langerhans Institute Dresden of Helmholtz Centre Munich at University Clinic Carl Gustav Carus of Technische Univeristät (TU) Dresden, Dresden, Germany.
Beissert S; Faculty of Medicine, Paul Langerhans Institute Dresden of Helmholtz Centre Munich at University Clinic Carl Gustav Carus of Technische Univeristät (TU) Dresden, Dresden, Germany.
Bonifacio E; Center for Regenerative Therapies Dresden, Faculty of Medicine Technische Universität (TU), Dresden, Germany.; Department of Dermatology, Faculty of Medicine, University Hospital Carl Gustav Carus of Technische Univeristät (TU) Dresden, Dresden, Germany.
Günther C; Faculty of Medicine, Paul Langerhans Institute Dresden of Helmholtz Centre Munich at University Clinic Carl Gustav Carus of Technische Univeristät (TU) Dresden, Dresden, Germany.
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Źródło:
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Frontiers in immunology [Front Immunol] 2022 Jul 13; Vol. 13, pp. 897500. Date of Electronic Publication: 2022 Jul 13 (Print Publication: 2022).
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Original Publication: [Lausanne : Frontiers Research Foundation]
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MeSH Terms:
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Dendritic Cells*/metabolism
Dendritic Cells*/pathology
Lupus Erythematosus, Cutaneous*/genetics
Lupus Erythematosus, Cutaneous*/pathology
Lupus Erythematosus, Discoid*/genetics
Lupus Erythematosus, Discoid*/pathology
Chilblains/genetics ; Exodeoxyribonucleases/genetics ; Humans ; Interferon Type I/pharmacology ; Phosphoproteins/genetics
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References:
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Contributed Indexing:
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Keywords: LMNA; Lamin A/C; SLE; Trex1; Type I interferons; dendritic Cells (DC); monogenic familial chilblain lupus
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Substance Nomenclature:
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0 (Interferon Type I)
0 (Phosphoproteins)
EC 3.1.- (Exodeoxyribonucleases)
EC 3.1.16.- (three prime repair exonuclease 1)
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SCR Disease Name:
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Chilblain lupus 1
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Entry Date(s):
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Date Created: 20220801 Date Completed: 20220802 Latest Revision: 20221215
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Update Code:
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20240105
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PubMed Central ID:
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PMC9327789
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DOI:
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10.3389/fimmu.2022.897500
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PMID:
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35911727
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Heterozygous TREX1 mutations are associated with monogenic familial chilblain lupus and represent a risk factor for developing systemic lupus erythematosus. These interferonopathies originate from chronic type I interferon stimulation due to sensing of inadequately accumulating nucleic acids. We here analysed the composition of dendritic cell (DC) subsets, central stimulators of immune responses, in patients with TREX1 deficiency. We performed single-cell RNA-sequencing of peripheral blood DCs and monocytes from two patients with familial chilblain lupus and heterozygous mutations in TREX1 and from controls. Type I interferon pathway genes were strongly upregulated in patients. Cell frequencies of the myeloid and plasmacytoid DC and of monocyte populations in patients and controls were similar, but we describe a novel DC subpopulation highly enriched in patients: a myeloid DC CD1C + subpopulation characterized by the expression of LMNA, EMP1 and a type I interferon- stimulated gene profile. The presence of this defined subpopulation was confirmed in a second cohort of patients and controls by flow cytometry, also revealing that an increased percentage of patient's cells in the subcluster express costimulatory molecules. We identified a novel type I interferon responsive myeloid DC subpopulation, that might be important for the perpetuation of TREX1-induced chilblain lupus and other type I interferonopathies.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Eugster, Müller, Gompf, Reinhardt, Lindner, Ashton, Zimmermann, Beissert, Bonifacio and Günther.)
Erratum in: Front Immunol. 2022 Nov 25;13:1094578. (PMID: 36518762)
