C-type lectin receptor expression is a hallmark of neutrophils infiltrating the skin in epidermolysis bullosa acquisita
Christian F. Guerrero-Juarez University of Illinois / Rush University Medical Center
Kyle T. Amber Rush University Medical Center
Christian D. Sadik University of Lübeck
Ralf J. Ludwig University of Lübeck
Katja Bieber University of Lübeck
University of Veterinary Medicine Vienna
Norito Ishii Kurume University
Takashi Hashimoto Osaka Metropolitan University Graduate School of Medicine
Maxim V. Frolov University of Illinois
Maria Sverdlov University of Illinois
Connor Cole Rush University Medical Center
Sripriya Murthy University of Lübeck
Jenny Gieseler-Tillmann University of Lübeck
Payal M. Patel Rush University Medical Center / Massachusetts General Hospital
Lei Bao University of Lübeck
Maria Paula Zappia University of Illinois
Paul Schilf University of Lübeck
Jing Li Rush University Medical Center
Frontiers Media Sa
Inflammatory epidermolysis bullosa acquisita (EBA) is characterized by a neutrophilic response to anti-type VII collagen (COL7) antibodies resulting in the development of skin inflammation and blistering. The antibody transfer model of EBA closely mirrors this EBA phenotype.To better understand the changes induced in neutrophils upon recruitment from peripheral blood into lesional skin in EBA, we performed single-cell RNA-sequencing of whole blood and skin dissociate to capture minimally perturbed neutrophils and characterize their transcriptome.Through this approach, we identified clear distinctions between circulating activated neutrophils and intradermal neutrophils. Most strikingly, the gene expression of multiple C-type lectin receptors, which have previously been reported to orchestrate host defense against fungi and select bacteria, were markedly dysregulated. After confirming the upregulation of Clec4n, Clec4d, and Clec4e in experimental EBA as well as in lesional skin from patients with inflammatory EBA, we performed functional studies in globally deficient Clec4e-/- and Clec4d-/- mice as well as in neutrophil-specific Clec4n-/- mice. Deficiency in these genes did not reduce disease in the EBA model.Collectively, our results suggest that while the upregulation of Clec4n, Clec4d, and Clec4e is a hallmark of activated dermal neutrophil populations, their individual contribution to the pathogenesis of EBA is dispensable.
Englisch
2023
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CC BY 4.0 - Creative Commons Namensnennung 4.0 International Lizenz.
CC BY 4.0 International
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Inflammation; Dectin-2