Thomas J F Pranzatelli, Paola Perez, Anson Ku, Bruno Matuck, Khoa Huynh, Shunsuke Sakai, Mehdi Abed, Shyh-Ing Jang, Eiko Yamada, Kalie Dominick, Zara Ahmed, Amanda Oliver, Rachael Wasikowski, Quinn T Easter, Alan N Baer, Eileen Pelayo, Zohreh Khavandgar, David E Kleiner, M Teresa Magone, Sarthak Gupta, Christopher Lessard, A Darise Farris, Peter D Burbelo, Daniel Martin, Robert J Morell, Changyu Zheng, Nicholas Rachmaninoff, Jose Maldonado-Ortiz, Xufeng Qu, Marit Aure, Mohammad H Dezfulian, Ross Lake, Sarah Teichmann, Daniel L Barber, Lam C Tsoi, Adam G Sowalsky, Katarzyna M Tyc, Jinze Liu, Johann Gudjonsson, Kevin M Byrd, Philip L F Johnson, John A Chiorini, Blake M Warner
{"title":"GZMK+CD8+ T cells Target A Specific Acinar Cell Type in Sjögren's Disease.","authors":"Thomas J F Pranzatelli, Paola Perez, Anson Ku, Bruno Matuck, Khoa Huynh, Shunsuke Sakai, Mehdi Abed, Shyh-Ing Jang, Eiko Yamada, Kalie Dominick, Zara Ahmed, Amanda Oliver, Rachael Wasikowski, Quinn T Easter, Alan N Baer, Eileen Pelayo, Zohreh Khavandgar, David E Kleiner, M Teresa Magone, Sarthak Gupta, Christopher Lessard, A Darise Farris, Peter D Burbelo, Daniel Martin, Robert J Morell, Changyu Zheng, Nicholas Rachmaninoff, Jose Maldonado-Ortiz, Xufeng Qu, Marit Aure, Mohammad H Dezfulian, Ross Lake, Sarah Teichmann, Daniel L Barber, Lam C Tsoi, Adam G Sowalsky, Katarzyna M Tyc, Jinze Liu, Johann Gudjonsson, Kevin M Byrd, Philip L F Johnson, John A Chiorini, Blake M Warner","doi":"10.21203/rs.3.rs-3601404/v1","DOIUrl":null,"url":null,"abstract":"<p><p>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 <i>PRR4+CST3+WFDC2</i>- seromucous acinar cells that are particularly targeted in SjD. Notably, <i>GZMK</i>+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.</p>","PeriodicalId":94282,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10775371/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Research square","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.21203/rs.3.rs-3601404/v1","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
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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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