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GZMK+CD8+ T cells Target A Specific Acinar Cell Type in Sjögren's Disease.
Pranzatelli, Thomas J F; Perez, Paola; Ku, Anson; Matuck, Bruno; Huynh, Khoa; Sakai, Shunsuke; Abed, Mehdi; Jang, Shyh-Ing; Yamada, Eiko; Dominick, Kalie; Ahmed, Zara; Oliver, Amanda; Wasikowski, Rachael; Easter, Quinn T; Baer, Alan N; Pelayo, Eileen; Khavandgar, Zohreh; Kleiner, David E; Magone, M Teresa; Gupta, Sarthak; Lessard, Christopher; Farris, A Darise; Burbelo, Peter D; Martin, Daniel; Morell, Robert J; Zheng, Changyu; Rachmaninoff, Nicholas; Maldonado-Ortiz, Jose; Qu, Xufeng; Aure, Marit; Dezfulian, Mohammad H; Lake, Ross; Teichmann, Sarah; Barber, Daniel L; Tsoi, Lam C; Sowalsky, Adam G; Tyc, Katarzyna M; Liu, Jinze; Gudjonsson, Johann; Byrd, Kevin M; Johnson, Philip L F; Chiorini, John A; Warner, Blake M.
Afiliación
  • Pranzatelli TJF; Adeno-Associated Virus Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
  • Perez P; Department of Biology, University of Maryland College Park, MD, USA.
  • Ku A; Salivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
  • Matuck B; Laboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Bethesda, MD, USA.
  • Huynh K; Lab of Oral & Craniofacial Innovation (LOCI), Department of Innovation & Technology Research, ADA Science & Research Institute, Gaithersburg, MD, USA.
  • Sakai S; Department of Biostatistics, Virginia Commonwealth University, VA, USA.
  • Abed M; T-lymphocyte Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Jang SI; Salivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
  • Yamada E; Salivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
  • Dominick K; Salivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
  • Ahmed Z; Salivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
  • Oliver A; Salivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
  • Wasikowski R; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • Easter QT; Department of Dermatology, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA.
  • Baer AN; Lab of Oral & Craniofacial Innovation (LOCI), Department of Innovation & Technology Research, ADA Science & Research Institute, Gaithersburg, MD, USA.
  • Pelayo E; Sjögren's Clinical Investigations Team, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
  • Khavandgar Z; Sjögren's Clinical Investigations Team, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
  • Kleiner DE; Salivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
  • Magone MT; Sjögren's Clinical Investigations Team, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
  • Gupta S; Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda MD, USA.
  • Lessard C; Consult Services Section, National Eye Institute, National Institutes of Health, Bethesda MD, USA.
  • Farris AD; Salivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
  • Burbelo PD; Lupus Clinical Trials Unit, National Institute of Arthritis and Musculoskeletal and Skin, Diseases, National Institutes of Health, Bethesda MD, USA.
  • Martin D; Genes & Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
  • Morell RJ; Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
  • Zheng C; Adeno-Associated Virus Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
  • Rachmaninoff N; Genomics and Computational Biology Core, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA.
  • Maldonado-Ortiz J; Genomics and Computational Biology Core, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA.
  • Qu X; Genomics and Computational Biology Core, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA.
  • Aure M; Department of Biology, University of Maryland College Park, MD, USA.
  • Dezfulian MH; Adeno-Associated Virus Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
  • Lake R; Salivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
  • Teichmann S; Sjögren's Clinical Investigations Team, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
  • Barber DL; Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
  • Tsoi LC; Matrix and Morphogenesis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
  • Sowalsky AG; Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • Tyc KM; Laboratory of Genitourinary Cancer Pathogenesis (LCGP) Microscopy Core Facility, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Bethesda, MD, USA.
  • Liu J; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • Gudjonsson J; T-lymphocyte Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Byrd KM; Department of Dermatology, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA.
  • Johnson PLF; Laboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Bethesda, MD, USA.
  • Chiorini JA; Department of Biostatistics, Virginia Commonwealth University, VA, USA.
  • Warner BM; Department of Biostatistics, Virginia Commonwealth University, VA, USA.
Res Sq ; 2024 Jul 11.
Article en En | MEDLINE | ID: mdl-38196575
ABSTRACT
Sjögren's Disease (SjD) is a systemic autoimmune disease without a clear etiology or effective therapy. Utilizing unbiased single-cell and spatial transcriptomics to analyze human minor salivary glands in health and disease we developed a comprehensive understanding of the cellular landscape of healthy salivary glands and how that landscape changes in SjD patients. We identified novel seromucous acinar cell types and identified a population of PRR4+CST3+WFDC2- seromucous acinar cells that are particularly targeted in SjD. Notably, GZMK+CD8 T cells, enriched in SjD, exhibited a cytotoxic phenotype and were physically associated with immune-engaged epithelial cells in disease. These findings shed light on the immune response's impact on transitioning acinar cells with high levels of secretion and explain the loss of this specific cell population in SjD. This study explores the complex interplay of varied cell types in the salivary glands and their role in the pathology of Sjögren's Disease.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Res Sq Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Res Sq Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos