Titel (eng)

C-type lectin receptor expression is a hallmark of neutrophils infiltrating the skin in epidermolysis bullosa acquisita

Autor*in

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

Thomas Rülicke   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

Verlag

Frontiers Media Sa

Beschreibung (eng)

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.

Sprache des Objekts

Englisch

Datum

2023

Rechte

Dieses Werk bzw. dieser Inhalt steht unter einer
CC BY 4.0 - Creative Commons Namensnennung 4.0 International Lizenz.

CC BY 4.0 International

http://creativecommons.org/licenses/by/4.0/

Klassifikation

Inflammation; Dectin-2

Mitglied in der/den Collection(s) (1)