Integrated single-cell chromatin and transcriptomic analyses of peripheral immune cells in patients with alopecia areata
IntroductionAlopecia areata (AA) is an autoimmune disorder characterized by non-scarring hair loss ranging from mild, self-limiting episodes to severe and chronic forms. While prior research has primarily focused on lesional skin, the contribution of systemic immune cells remains underexplored.Metho...
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Frontiers Media S.A.
2025-07-01
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| author | Jesus Gay-Mimbrera Pedro Jesús Gómez-Arias Pedro Jesús Gómez-Arias Pablo Álvarez-Heredia Alexander Batista-Duharte Irene Rivera-Ruiz Macarena Aguilar-Luque Miguel Juan-Cencerrado Miguel Juan-Cencerrado Carmen Mochón-Jiménez Carmen Mochón-Jiménez Álvaro Cebrián-García Eloísa Andújar-Pulido Mónica Pérez-Alegre Alejandra Pera Alejandra Pera Juan Ruano Juan Ruano Juan Ruano |
| author_facet | Jesus Gay-Mimbrera Pedro Jesús Gómez-Arias Pedro Jesús Gómez-Arias Pablo Álvarez-Heredia Alexander Batista-Duharte Irene Rivera-Ruiz Macarena Aguilar-Luque Miguel Juan-Cencerrado Miguel Juan-Cencerrado Carmen Mochón-Jiménez Carmen Mochón-Jiménez Álvaro Cebrián-García Eloísa Andújar-Pulido Mónica Pérez-Alegre Alejandra Pera Alejandra Pera Juan Ruano Juan Ruano Juan Ruano |
| author_sort | Jesus Gay-Mimbrera |
| collection | DOAJ |
| description | IntroductionAlopecia areata (AA) is an autoimmune disorder characterized by non-scarring hair loss ranging from mild, self-limiting episodes to severe and chronic forms. While prior research has primarily focused on lesional skin, the contribution of systemic immune cells remains underexplored.MethodsWe performed integrated single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) on peripheral blood mononuclear cells (PBMCs) from patients with mild and severe AA, as well as healthy controls. A total of 32,453 high-quality cells were analyzed across 36 immune cell subtypes.ResultsIn AA patients, especially those with severe disease, we observed increased transcriptional heterogeneity, cytokine and chemokine pathway activation, and upregulation of antigen-presentation machinery enriched in TH1, TH2, and TH17 signatures. Chromatin accessibility profiling revealed 42,248 significant peaks with pronounced epigenetic remodeling in CD14+ monocytes, NK cells, and CD8+ T cells. Mild AA showed early immune regulatory failure, with elevated exhaustion markers in double-negative T cells and increased apoptosis in myeloid populations. Pseudotime and transcription factor analyses indicated altered differentiation trajectories, and inferred cell-cell communication networks highlighted monocytes, NK cells, and memory T cells as key signaling hubs.DiscussionOur results provide the first integrated single-cell chromatin and transcriptomic map of peripheral immune dysregulation in AA. These findings uncover systemic alterations associated with disease severity and identify candidate pathways for immune modulation and therapeutic targeting. |
| format | Article |
| id | doaj-art-cca6efea7f214d829238a6c1968d525e |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-cca6efea7f214d829238a6c1968d525e2025-08-20T02:37:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.15652411565241Integrated single-cell chromatin and transcriptomic analyses of peripheral immune cells in patients with alopecia areataJesus Gay-Mimbrera0Pedro Jesús Gómez-Arias1Pedro Jesús Gómez-Arias2Pablo Álvarez-Heredia3Alexander Batista-Duharte4Irene Rivera-Ruiz5Macarena Aguilar-Luque6Miguel Juan-Cencerrado7Miguel Juan-Cencerrado8Carmen Mochón-Jiménez9Carmen Mochón-Jiménez10Álvaro Cebrián-García11Eloísa Andújar-Pulido12Mónica Pérez-Alegre13Alejandra Pera14Alejandra Pera15Juan Ruano16Juan Ruano17Juan Ruano18Inflammatory Immune-Mediated Chronic Skin Diseases Laboratory (GC26), Maimonides Biomedical Research Institute of Cordoba (IMIBIC)/University of Cordoba/Reina Sofia University Hospital, Córdoba, SpainInflammatory Immune-Mediated Chronic Skin Diseases Laboratory (GC26), Maimonides Biomedical Research Institute of Cordoba (IMIBIC)/University of Cordoba/Reina Sofia University Hospital, Córdoba, SpainDepartment of Dermatology, Reina Sofía University Hospital, Córdoba, SpainImmunology and Allergy Group (GC01), Maimonides Biomedical Research Institute of Cordoba (IMIBIC)/University of Cordoba/Reina Sofia University Hospital, Cordoba, SpainImmunology and Allergy Group (GC01), Maimonides Biomedical Research Institute of Cordoba (IMIBIC)/University of Cordoba/Reina Sofia University Hospital, Cordoba, SpainDepartment of Dermatology, Reina Sofía University Hospital, Córdoba, SpainInflammatory Immune-Mediated Chronic Skin Diseases Laboratory (GC26), Maimonides Biomedical Research Institute of Cordoba (IMIBIC)/University of Cordoba/Reina Sofia University Hospital, Córdoba, SpainInflammatory Immune-Mediated Chronic Skin Diseases Laboratory (GC26), Maimonides Biomedical Research Institute of Cordoba (IMIBIC)/University of Cordoba/Reina Sofia University Hospital, Córdoba, SpainDepartment of Dermatology, Reina Sofía University Hospital, Córdoba, SpainInflammatory Immune-Mediated Chronic Skin Diseases Laboratory (GC26), Maimonides Biomedical Research Institute of Cordoba (IMIBIC)/University of Cordoba/Reina Sofia University Hospital, Córdoba, SpainDepartment of Dermatology, Reina Sofía University Hospital, Córdoba, SpainInflammatory Immune-Mediated Chronic Skin Diseases Laboratory (GC26), Maimonides Biomedical Research Institute of Cordoba (IMIBIC)/University of Cordoba/Reina Sofia University Hospital, Córdoba, SpainGenomic Unit, Andalusian Molecular Biology and Regenerative Medicine Center (CABIMER), CSIC-University of Seville-University Pablo de Olavide, Seville, SpainGenomic Unit, Andalusian Molecular Biology and Regenerative Medicine Center (CABIMER), CSIC-University of Seville-University Pablo de Olavide, Seville, SpainImmunology and Allergy Group (GC01), Maimonides Biomedical Research Institute of Cordoba (IMIBIC)/University of Cordoba/Reina Sofia University Hospital, Cordoba, SpainDepartment of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, SpainInflammatory Immune-Mediated Chronic Skin Diseases Laboratory (GC26), Maimonides Biomedical Research Institute of Cordoba (IMIBIC)/University of Cordoba/Reina Sofia University Hospital, Córdoba, SpainImmunology and Allergy Group (GC01), Maimonides Biomedical Research Institute of Cordoba (IMIBIC)/University of Cordoba/Reina Sofia University Hospital, Cordoba, SpainDepartment of Medicine, University of Córdoba, Córdoba, SpainIntroductionAlopecia areata (AA) is an autoimmune disorder characterized by non-scarring hair loss ranging from mild, self-limiting episodes to severe and chronic forms. While prior research has primarily focused on lesional skin, the contribution of systemic immune cells remains underexplored.MethodsWe performed integrated single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) on peripheral blood mononuclear cells (PBMCs) from patients with mild and severe AA, as well as healthy controls. A total of 32,453 high-quality cells were analyzed across 36 immune cell subtypes.ResultsIn AA patients, especially those with severe disease, we observed increased transcriptional heterogeneity, cytokine and chemokine pathway activation, and upregulation of antigen-presentation machinery enriched in TH1, TH2, and TH17 signatures. Chromatin accessibility profiling revealed 42,248 significant peaks with pronounced epigenetic remodeling in CD14+ monocytes, NK cells, and CD8+ T cells. Mild AA showed early immune regulatory failure, with elevated exhaustion markers in double-negative T cells and increased apoptosis in myeloid populations. Pseudotime and transcription factor analyses indicated altered differentiation trajectories, and inferred cell-cell communication networks highlighted monocytes, NK cells, and memory T cells as key signaling hubs.DiscussionOur results provide the first integrated single-cell chromatin and transcriptomic map of peripheral immune dysregulation in AA. These findings uncover systemic alterations associated with disease severity and identify candidate pathways for immune modulation and therapeutic targeting.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1565241/fullAlopecia areataseverityperipheral bloodimmune cellssingle-cell RNA sequencingchromatin accessibility |
| spellingShingle | Jesus Gay-Mimbrera Pedro Jesús Gómez-Arias Pedro Jesús Gómez-Arias Pablo Álvarez-Heredia Alexander Batista-Duharte Irene Rivera-Ruiz Macarena Aguilar-Luque Miguel Juan-Cencerrado Miguel Juan-Cencerrado Carmen Mochón-Jiménez Carmen Mochón-Jiménez Álvaro Cebrián-García Eloísa Andújar-Pulido Mónica Pérez-Alegre Alejandra Pera Alejandra Pera Juan Ruano Juan Ruano Juan Ruano Integrated single-cell chromatin and transcriptomic analyses of peripheral immune cells in patients with alopecia areata Frontiers in Immunology Alopecia areata severity peripheral blood immune cells single-cell RNA sequencing chromatin accessibility |
| title | Integrated single-cell chromatin and transcriptomic analyses of peripheral immune cells in patients with alopecia areata |
| title_full | Integrated single-cell chromatin and transcriptomic analyses of peripheral immune cells in patients with alopecia areata |
| title_fullStr | Integrated single-cell chromatin and transcriptomic analyses of peripheral immune cells in patients with alopecia areata |
| title_full_unstemmed | Integrated single-cell chromatin and transcriptomic analyses of peripheral immune cells in patients with alopecia areata |
| title_short | Integrated single-cell chromatin and transcriptomic analyses of peripheral immune cells in patients with alopecia areata |
| title_sort | integrated single cell chromatin and transcriptomic analyses of peripheral immune cells in patients with alopecia areata |
| topic | Alopecia areata severity peripheral blood immune cells single-cell RNA sequencing chromatin accessibility |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1565241/full |
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