C-type lectin receptor expression is a hallmark of neutrophils infiltrating the skin in epidermolysis bullosa acquisita
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 bet...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1266359/full |
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| author | Christian F. Guerrero-Juarez Christian F. Guerrero-Juarez Paul Schilf Jing Li Maria Paula Zappia Lei Bao Payal M. Patel Payal M. Patel Jenny Gieseler-Tillmann Sripriya Murthy Connor Cole Maria Sverdlov Maxim V. Frolov Takashi Hashimoto Norito Ishii Thomas Rülicke Katja Bieber Katja Bieber Ralf J. Ludwig Ralf J. Ludwig Christian D. Sadik Kyle T. Amber Kyle T. Amber |
| author_facet | Christian F. Guerrero-Juarez Christian F. Guerrero-Juarez Paul Schilf Jing Li Maria Paula Zappia Lei Bao Payal M. Patel Payal M. Patel Jenny Gieseler-Tillmann Sripriya Murthy Connor Cole Maria Sverdlov Maxim V. Frolov Takashi Hashimoto Norito Ishii Thomas Rülicke Katja Bieber Katja Bieber Ralf J. Ludwig Ralf J. Ludwig Christian D. Sadik Kyle T. Amber Kyle T. Amber |
| author_sort | Christian F. Guerrero-Juarez |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T23:11:12Z |
| format | Article |
| id | doaj.art-1405ecc563cf4c7cb34962308c3e35d5 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T23:11:12Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-1405ecc563cf4c7cb34962308c3e35d52023-09-21T07:50:09ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-09-011410.3389/fimmu.2023.12663591266359C-type lectin receptor expression is a hallmark of neutrophils infiltrating the skin in epidermolysis bullosa acquisitaChristian F. Guerrero-Juarez0Christian F. Guerrero-Juarez1Paul Schilf2Jing Li3Maria Paula Zappia4Lei Bao5Payal M. Patel6Payal M. Patel7Jenny Gieseler-Tillmann8Sripriya Murthy9Connor Cole10Maria Sverdlov11Maxim V. Frolov12Takashi Hashimoto13Norito Ishii14Thomas Rülicke15Katja Bieber16Katja Bieber17Ralf J. Ludwig18Ralf J. Ludwig19Christian D. Sadik20Kyle T. Amber21Kyle T. Amber22Carle Illinois College of Medicine, University of Illinois, Urbana-Champaign, Urbana, IL, United StatesDepartment of Dermatology, Rush University Medical Center, Chicago, IL, United StatesDepartment of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, GermanyDepartment of Dermatology, Rush University Medical Center, Chicago, IL, United StatesDepartment of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL, United StatesDepartment of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, GermanyDepartment of Dermatology, Rush University Medical Center, Chicago, IL, United StatesDepartment of Dermatology, Massachusetts General Hospital, Boston, MA, United StatesDepartment of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, GermanyDepartment of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, GermanyDepartment of Dermatology, Rush University Medical Center, Chicago, IL, United StatesResearch Histology Core, University of Illinois at Chicago, Chicago, IL, United StatesDepartment of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL, United StatesDepartment of Dermatology, Osaka Metropolitan University Graduate School of Medicine, Osaka, JapanDepartment of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, JapanDepartment of Biomedical Sciences and Ludwig Boltzmann Institute for Hematology and Oncology, University of Veterinary Medicine Vienna, Vienna, AustriaDepartment of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, Germany0Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, GermanyDepartment of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, Germany0Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, GermanyDepartment of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, GermanyDepartment of Dermatology, Rush University Medical Center, Chicago, IL, United States1Department of Internal Medicine, Rush University Medical Center, Chicago, IL, United StatesIntroductionInflammatory 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1266359/fullepidermolysis bullosa acquisitapemphigoidneutrophilsingle cell RNA seqC-type lectin receptor (CLRs) |
| spellingShingle | Christian F. Guerrero-Juarez Christian F. Guerrero-Juarez Paul Schilf Jing Li Maria Paula Zappia Lei Bao Payal M. Patel Payal M. Patel Jenny Gieseler-Tillmann Sripriya Murthy Connor Cole Maria Sverdlov Maxim V. Frolov Takashi Hashimoto Norito Ishii Thomas Rülicke Katja Bieber Katja Bieber Ralf J. Ludwig Ralf J. Ludwig Christian D. Sadik Kyle T. Amber Kyle T. Amber C-type lectin receptor expression is a hallmark of neutrophils infiltrating the skin in epidermolysis bullosa acquisita Frontiers in Immunology epidermolysis bullosa acquisita pemphigoid neutrophil single cell RNA seq C-type lectin receptor (CLRs) |
| title | C-type lectin receptor expression is a hallmark of neutrophils infiltrating the skin in epidermolysis bullosa acquisita |
| title_full | C-type lectin receptor expression is a hallmark of neutrophils infiltrating the skin in epidermolysis bullosa acquisita |
| title_fullStr | C-type lectin receptor expression is a hallmark of neutrophils infiltrating the skin in epidermolysis bullosa acquisita |
| title_full_unstemmed | C-type lectin receptor expression is a hallmark of neutrophils infiltrating the skin in epidermolysis bullosa acquisita |
| title_short | C-type lectin receptor expression is a hallmark of neutrophils infiltrating the skin in epidermolysis bullosa acquisita |
| title_sort | c type lectin receptor expression is a hallmark of neutrophils infiltrating the skin in epidermolysis bullosa acquisita |
| topic | epidermolysis bullosa acquisita pemphigoid neutrophil single cell RNA seq C-type lectin receptor (CLRs) |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1266359/full |
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