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

Frontiers in Immunology

Immunology

Christian F. Guerrero-Juarez¹  Maxim V. Frolov²  Maria Paula Zappia²  Thomas Rülicke³  Christian D. Sadik⁴  Paul Schilf⁴  Jenny Gieseler-Tillmann⁴  Sripriya Murthy⁴  Lei Bao⁴  Katja Bieber⁵  Ralf J. Ludwig⁵  Norito Ishii⁶  Takashi Hashimoto⁷  Connor Cole⁸  Jing Li⁸  Payal M. Patel⁹  Kyle T. Amber^1,10  Maria Sverdlov^1,11 

[1]Carle Illinois College of Medicine, University of Illinois, Urbana-Champaign, Urbana, IL, United States

[2]Department of Dermatology, Rush University Medical Center, Chicago, IL, United States

[3]Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL, United States

[4]Department of Biomedical Sciences and Ludwig Boltzmann Institute for Hematology and Oncology, University of Veterinary Medicine Vienna, Vienna, Austria

[5]Department of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, Germany

[6]Department of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, Germany

[7]Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany

[8]Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Japan

[9]Department of Dermatology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan

[10]Department of Dermatology, Rush University Medical Center, Chicago, IL, United States

[11]Department of Dermatology, Rush University Medical Center, Chicago, IL, United States

[12]Department of Dermatology, Massachusetts General Hospital, Boston, MA, United States

[13]Department of Dermatology, Rush University Medical Center, Chicago, IL, United States

[14]Department of Internal Medicine, Rush University Medical Center, Chicago, IL, United States

[15]Research Histology Core, University of Illinois at Chicago, Chicago, IL, United States

关键词: epidermolysis bullosa acquisita;    pemphigoid;    neutrophil;    single cell RNA seq;    C-type lectin receptor (CLRs);   

DOI  :  10.3389/fimmu.2023.1266359

 received in 2023-07-24, accepted in 2023-08-31,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionInflammatory 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.MethodsTo 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.ResultsThrough 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.DiscussionCollectively, 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.

【 授权许可】

Unknown   
Copyright © 2023 Guerrero-Juarez, Schilf, Li, Zappia, Bao, Patel, Gieseler-Tillmann, Murthy, Cole, Sverdlov, Frolov, Hashimoto, Ishii, Rülicke, Bieber, Ludwig, Sadik and Amber