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Eugster, A.* ; Müller, D.* ; Gompf, A.* ; Reinhardt, S.* ; Lindner, A.* ; Ashton, M.P.* ; Zimmermann, N.* ; Beissert, S.* ; Bonifacio, E. ; Günther, C.*

A novel type I interferon primed dendritic cell subpopulation in TREX1 mutant chilblain lupus patients.

Front. Immunol. 13:897500 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Dendritic Cells (dc) ; Lamin A/c ; Lmna ; Monogenic Familial Chilblain Lupus ; Sle ; Trex1 ; Type I Interferons
ISSN (print) / ISBN 1664-3224
e-ISSN 1664-3224
Zeitschrift Frontiers in Immunology
Quellenangaben Band: 13, Heft: , Seiten: , Artikelnummer: 897500 Supplement: ,
Verlag Frontiers
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Pancreatic Islet Research (IPI)
Förderungen Zentrum für Regenerative Therapien Dresden
Deutsche Forschungsgemeinschaft