phaidra.vetmeduni.ac.at o:2639 DOI 10.3389/fimmu.2023.1266359 C-type lectin receptor expression is a hallmark of neutrophils infiltrating the skin in epidermolysis bullosa acquisita 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. eng Inflammation; Dectin-2 2024-02-27T10:32:32.358Z LOMv1.0 Author BEGIN:VCARD VERSION:3.0 N:Guerrero-Juarez;Christian F.; FN:Christian F. Guerrero-Juarez END:VCARD BEGIN:VCARD VERSION:3.0 N:Amber;Kyle T.; FN:Kyle T. Amber END:VCARD BEGIN:VCARD VERSION:3.0 N:Sadik;Christian D.; FN:Christian D. Sadik END:VCARD BEGIN:VCARD VERSION:3.0 N:Ludwig;Ralf J.; FN:Ralf J. Ludwig END:VCARD BEGIN:VCARD VERSION:3.0 N:Bieber;Katja; FN:Katja Bieber END:VCARD BEGIN:VCARD VERSION:3.0 N:Rülicke;Thomas; FN:Thomas Rülicke X-ORCID:https://orcid.org/0000-0002-2121-9496 END:VCARD BEGIN:VCARD VERSION:3.0 N:Ishii;Norito; FN:Norito Ishii END:VCARD BEGIN:VCARD VERSION:3.0 N:Hashimoto;Takashi; FN:Takashi Hashimoto END:VCARD BEGIN:VCARD VERSION:3.0 N:Frolov;Maxim V.; FN:Maxim V. Frolov END:VCARD BEGIN:VCARD VERSION:3.0 N:Sverdlov;Maria; FN:Maria Sverdlov END:VCARD BEGIN:VCARD VERSION:3.0 N:Cole;Connor; FN:Connor Cole END:VCARD BEGIN:VCARD VERSION:3.0 N:Murthy;Sripriya; FN:Sripriya Murthy END:VCARD BEGIN:VCARD VERSION:3.0 N:Gieseler-Tillmann;Jenny; FN:Jenny Gieseler-Tillmann END:VCARD BEGIN:VCARD VERSION:3.0 N:Patel;Payal M.; FN:Payal M. Patel END:VCARD BEGIN:VCARD VERSION:3.0 N:Bao;Lei; FN:Lei Bao END:VCARD BEGIN:VCARD VERSION:3.0 N:Zappia;Maria Paula; FN:Maria Paula Zappia END:VCARD BEGIN:VCARD VERSION:3.0 N:Schilf;Paul; FN:Paul Schilf END:VCARD BEGIN:VCARD VERSION:3.0 N:Li;Jing; FN:Jing Li END:VCARD https://w3id.org/kim/hcrt/scheme https://w3id.org/kim/hcrt/text Textdokument Text LOMv1.0 yes https://creativecommons.org/licenses/by/4.0 application/pdf 6562441 https://phaidra.vetmeduni.ac.at/o:2639 https://phaidra.vetmeduni.ac.at/api/object/o:2639/thumbnail LOMv1.0 discipline