GZMK+CD8+ T cells target a specific acinar cell type in Sjögren's disease
Using single-cell and spatial transcriptomics and proteomics, this study identifies a selective loss of PRR4⁺CST3⁺WFDC2⁻ seromucous acinar cells and a rise in GZMK⁺CD8⁺ T cells in Sjögren's disease, revealing distinct immune-mediated epithelial remodeling and interferon-driven dysfunction across diverse clinical presentations. These findings uncover a novel sub-cytolytic effector mechanism by which GZMK⁺CD8⁺ T cells impair mitochondrial integrity and activate innate immune signaling, linking epithelial injury to type I interferon responses and offering new therapeutic targets.
Authors
- Sarthak Gupta (ORCID: https://orcid.org/0000-0001-8255-3554)
- Quinn T. Easter (ORCID: https://orcid.org/0000-0002-8018-0405)
- Mehdi Abed
- Marit H. Aure (ORCID: https://orcid.org/0000-0002-2080-1740)
- Robert J. Morell (ORCID: https://orcid.org/0000-0003-1537-7356)
- Thomas Pranzatelli (ORCID: https://orcid.org/0000-0002-5763-1036)
- Alan N. Baer (ORCID: https://orcid.org/0000-0001-8344-013X)
- Daniel Martı́n (ORCID: https://orcid.org/0000-0002-8880-9087)
- David E. Kleiner (ORCID: https://orcid.org/0000-0003-3442-4453)
- Philip L. Johnson
- Anson T. Ku (ORCID: https://orcid.org/0000-0002-6471-5502)
- Sarah Amalia Teichmann (ORCID: https://orcid.org/0000-0002-6294-6366)
- Katarzyna M. Tyc (ORCID: https://orcid.org/0000-0002-3850-6934)
- Zara Ahmed (ORCID: https://orcid.org/0009-0008-0411-2401)
- Paola Pérez (ORCID: https://orcid.org/0000-0002-1695-5763)
- Adam G. Sowalsky (ORCID: https://orcid.org/0000-0003-2760-1853)
- Peter D. Burbelo (ORCID: https://orcid.org/0000-0003-1717-048X)
- Ross Lake (ORCID: https://orcid.org/0000-0002-6929-0793)
- M Dezfulian (ORCID: https://orcid.org/0000-0001-9979-5365)
- Xufeng Qu
- Blake M. Warner (ORCID: https://orcid.org/0000-0002-4961-018X)
- Amanda J. Oliver (ORCID: https://orcid.org/0000-0003-1690-9027)
- Khoa Huynh (ORCID: https://orcid.org/0000-0001-5374-6111)
- M. Teresa Magone (ORCID: https://orcid.org/0000-0001-6370-6295)
- A. Darise Farris (ORCID: https://orcid.org/0000-0003-3009-2017)
- John A. Chiorini (ORCID: https://orcid.org/0000-0003-4919-4056)
- Daniel L. Barber (ORCID: https://orcid.org/0000-0001-7008-7509)
- Lam C. Tsoi (ORCID: https://orcid.org/0000-0003-1627-5722)
- Johann Eli Gudjonsson (ORCID: https://orcid.org/0000-0002-0080-0812)
- Kevin M. Byrd (ORCID: https://orcid.org/0000-0002-5565-0524)
- Nicholas Rachmaninoff (ORCID: https://orcid.org/0000-0002-3228-3610)
- Christopher J. Lessard (ORCID: https://orcid.org/0000-0003-2440-3843)
- Eiko Yamada (ORCID: https://orcid.org/0000-0001-9899-8726)
- Eileen Pelayo
- Zohreh Khavandgar
- Bruno Fernandes Matuck (ORCID: https://orcid.org/0000-0002-2132-3402)
- Kalie Dominick
- Jose Maldonado-Ortiz
- Rachael Bogle (ORCID: https://orcid.org/0000-0003-3544-3023)
- Shunsuke Sakai (ORCID: https://orcid.org/0000-0003-0344-9447)
- Jinze Liu (ORCID: https://orcid.org/0000-0003-0555-9412)
- Changyu Zheng
- Shyh-Ing Jang
Institutions
- National Institutes of Health (US)
- Harvard University (US)
- Virginia Commonwealth University (US)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- Wellcome Sanger Institute (GB)
- Oklahoma Medical Research Foundation (US)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (US)
- National Institute of Dental and Craniofacial Research (US)
- Michigan Medicine (US)
- National Institute of Allergy and Infectious Diseases (US)
- National Eye Institute (US)
- National Cancer Institute (US)
- Institut de Recherche et d’Innovation (FR)
- Center for Cancer Research (US)
- National Institute on Deafness and Other Communication Disorders (US)
- University of Maryland, College Park (US)
Publication Details
- Journal
- Annals of the Rheumatic Diseases
- Published
- 2025-10-01
- DOI
- https://doi.org/10.1016/j.ard.2025.08.014
- Citations
- 5
- Primary Topic
- Salivary Gland Disorders and Functions
- Type
- article
- Field-Weighted Citation Impact
- 5.82
Funders
- National Institutes of Health
- National Cancer Institute
- National Institute of Dental and Craniofacial Research