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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)
Publ. Version/Full Text Research data 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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords 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
Journal Frontiers in Immunology
Quellenangaben Volume: 13, Issue: , Pages: , Article Number: 897500 Supplement: ,
Publisher Frontiers
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Pancreatic Islet Research (IPI)
Grants Zentrum für Regenerative Therapien Dresden
Deutsche Forschungsgemeinschaft