C-type lectin receptor expression is a hallmark of neutrophils infiltrating the skin in epidermolysis bullosa acquisita.
Christian F Guerrero-Juarez, Paul Schilf, Jing Li, Maria Paula Zappia, Lei Bao, Payal M Patel, Jenny Gieseler-Tillmann, Sripriya Murthy, Connor Cole, Maria Sverdlov, Maxim V Frolov, Takashi Hashimoto, Norito Ishii, Thomas Rülicke, Katja Bieber, Ralf J Ludwig, Christian D Sadik, Kyle T Amber
Author Information
Christian F Guerrero-Juarez: Carle Illinois College of Medicine, University of Illinois, Urbana-Champaign, Urbana, IL, United States.
Paul Schilf: Department of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, Germany.
Jing Li: Department of Dermatology, Rush University Medical Center, Chicago, IL, United States.
Maria Paula Zappia: Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL, United States.
Lei Bao: Department of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, Germany.
Payal M Patel: Department of Dermatology, Rush University Medical Center, Chicago, IL, United States.
Jenny Gieseler-Tillmann: Department of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, Germany.
Sripriya Murthy: Department of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, Germany.
Connor Cole: Department of Dermatology, Rush University Medical Center, Chicago, IL, United States.
Maria Sverdlov: Research Histology Core, University of Illinois at Chicago, Chicago, IL, United States.
Maxim V Frolov: Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL, United States.
Takashi Hashimoto: Department of Dermatology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
Norito Ishii: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Japan.
Thomas Rülicke: Department of Biomedical Sciences and Ludwig Boltzmann Institute for Hematology and Oncology, University of Veterinary Medicine Vienna, Vienna, Austria.
Katja Bieber: Department of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, Germany.
Ralf J Ludwig: Department of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, Germany.
Christian D Sadik: Department of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, Germany.
Kyle T Amber: Department of Dermatology, Rush University Medical Center, Chicago, IL, United States.
Introduction: 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. Methods: 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. Results: 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 , , and in experimental EBA as well as in lesional skin from patients with inflammatory EBA, we performed functional studies in globally deficient and mice as well as in neutrophil-specific mice. Deficiency in these genes did not reduce disease in the EBA model. Discussion: Collectively, our results suggest that while the upregulation of , , and is a hallmark of activated dermal neutrophil populations, their individual contribution to the pathogenesis of EBA is dispensable.
