Systems immunology integrates the complex endotypes of recessive dystrophic epidermolysis bullosa
Abstract Endotypes are characterized by the immunological, inflammatory, metabolic, and remodelling pathways that explain the mechanisms underlying the clinical presentation (phenotype) of a disease. Recessive dystrophic epidermolysis bullosa (RDEB) is a severe blistering disease caused by COL7A1 pa...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-55934-7 |
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| author | Nell Hirt Enzo Manchon Qian Chen Clara Delaroque Aurelien Corneau Patrice Hemon Safaa Saker-Delye Pauline Bataille Jean-David Bouaziz Emmanuelle Bourrat Alain Hovnanian Helene Le Buanec Fawzi Aoudjit Hicham El Costa Nabila Jabrane-Ferrat Reem Al-Daccak |
| author_facet | Nell Hirt Enzo Manchon Qian Chen Clara Delaroque Aurelien Corneau Patrice Hemon Safaa Saker-Delye Pauline Bataille Jean-David Bouaziz Emmanuelle Bourrat Alain Hovnanian Helene Le Buanec Fawzi Aoudjit Hicham El Costa Nabila Jabrane-Ferrat Reem Al-Daccak |
| author_sort | Nell Hirt |
| collection | DOAJ |
| description | Abstract Endotypes are characterized by the immunological, inflammatory, metabolic, and remodelling pathways that explain the mechanisms underlying the clinical presentation (phenotype) of a disease. Recessive dystrophic epidermolysis bullosa (RDEB) is a severe blistering disease caused by COL7A1 pathogenic variants. Although underscored by animal studies, the endotypes of human RDEB are poorly understood. To fill this gap, we apply systems immunology approaches using single-cell high-dimensional techniques to capture the signature of peripheral immune cells and the diversity of metabolic profiles in RDEB adults, sampled outside of any opportunistic infection and active cancer. Our study, demonstrates the particular inflammation and immunity characteristics of RDEB adults, with activated / effector T and dysfunctional natural killer cell signatures, concomitant with an overall pro-inflammatory lipid signature. Artificial intelligence prediction models and principal component analysis stress that RDEB is not solely confined to cutaneous issues but has complex systemic endotypes marked by immune dysregulation and hyperinflammation. By characterising the phenotype-endotype association in RDEB adults, our study lays the groundwork for translational interventions that could by lessening inflammation, alleviate the everlasting suffering of RDEB patients, while awaiting curative genetic therapies. |
| format | Article |
| id | doaj-art-28e074669d214654a235e19c38b238db |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-28e074669d214654a235e19c38b238db2025-01-19T12:32:08ZengNature PortfolioNature Communications2041-17232025-01-0116111810.1038/s41467-025-55934-7Systems immunology integrates the complex endotypes of recessive dystrophic epidermolysis bullosaNell Hirt0Enzo Manchon1Qian Chen2Clara Delaroque3Aurelien Corneau4Patrice Hemon5Safaa Saker-Delye6Pauline Bataille7Jean-David Bouaziz8Emmanuelle Bourrat9Alain Hovnanian10Helene Le Buanec11Fawzi Aoudjit12Hicham El Costa13Nabila Jabrane-Ferrat14Reem Al-Daccak15National Institute of Health and Medical Research (INSERM) UMRS-976 HIPI, Paris Cité University, Saint-Louis HospitalNational Institute of Health and Medical Research (INSERM) UMRS-976 HIPI, Paris Cité University, Saint-Louis HospitalBoston Childrens Hospital, Harvard Medical SchoolINSERM U1016, The National Centre for Scientific Research (CNRS) UMR 8104, Paris Cité UniversityPitié-Salpêtrière Cytometry, UMS037, Sorbonne UniversityLBAI, INSERM UMR1227, Brest UniversityGenethonDermatology Department, AP-HP, Saint-Louis HospitalNational Institute of Health and Medical Research (INSERM) UMRS-976 HIPI, Paris Cité University, Saint-Louis HospitalDermatology Department, AP-HP, Saint-Louis HospitalLaboratory of Genetic Skin Diseases, Imagine Institute, Paris Cité University, INSERM UMR 1163National Institute of Health and Medical Research (INSERM) UMRS-976 HIPI, Paris Cité University, Saint-Louis HospitalDivision of Immune and Infectious Diseases, CHU de Quebec Research Centre, Department of Microbiology-Infectiology and Immunology, Faculty of Medicine, Laval UniversityInstitute for Infectious and Inflammatory Diseases, CNRS UMR5051, INSERM UMR1291, Toulouse III UniversityInstitute for Infectious and Inflammatory Diseases, CNRS UMR5051, INSERM UMR1291, Toulouse III UniversityNational Institute of Health and Medical Research (INSERM) UMRS-976 HIPI, Paris Cité University, Saint-Louis HospitalAbstract Endotypes are characterized by the immunological, inflammatory, metabolic, and remodelling pathways that explain the mechanisms underlying the clinical presentation (phenotype) of a disease. Recessive dystrophic epidermolysis bullosa (RDEB) is a severe blistering disease caused by COL7A1 pathogenic variants. Although underscored by animal studies, the endotypes of human RDEB are poorly understood. To fill this gap, we apply systems immunology approaches using single-cell high-dimensional techniques to capture the signature of peripheral immune cells and the diversity of metabolic profiles in RDEB adults, sampled outside of any opportunistic infection and active cancer. Our study, demonstrates the particular inflammation and immunity characteristics of RDEB adults, with activated / effector T and dysfunctional natural killer cell signatures, concomitant with an overall pro-inflammatory lipid signature. Artificial intelligence prediction models and principal component analysis stress that RDEB is not solely confined to cutaneous issues but has complex systemic endotypes marked by immune dysregulation and hyperinflammation. By characterising the phenotype-endotype association in RDEB adults, our study lays the groundwork for translational interventions that could by lessening inflammation, alleviate the everlasting suffering of RDEB patients, while awaiting curative genetic therapies.https://doi.org/10.1038/s41467-025-55934-7 |
| spellingShingle | Nell Hirt Enzo Manchon Qian Chen Clara Delaroque Aurelien Corneau Patrice Hemon Safaa Saker-Delye Pauline Bataille Jean-David Bouaziz Emmanuelle Bourrat Alain Hovnanian Helene Le Buanec Fawzi Aoudjit Hicham El Costa Nabila Jabrane-Ferrat Reem Al-Daccak Systems immunology integrates the complex endotypes of recessive dystrophic epidermolysis bullosa Nature Communications |
| title | Systems immunology integrates the complex endotypes of recessive dystrophic epidermolysis bullosa |
| title_full | Systems immunology integrates the complex endotypes of recessive dystrophic epidermolysis bullosa |
| title_fullStr | Systems immunology integrates the complex endotypes of recessive dystrophic epidermolysis bullosa |
| title_full_unstemmed | Systems immunology integrates the complex endotypes of recessive dystrophic epidermolysis bullosa |
| title_short | Systems immunology integrates the complex endotypes of recessive dystrophic epidermolysis bullosa |
| title_sort | systems immunology integrates the complex endotypes of recessive dystrophic epidermolysis bullosa |
| url | https://doi.org/10.1038/s41467-025-55934-7 |
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