GZMK⁺CD8⁺ T Cells Induce Acinar Cell Senescence and Salivary Secretion Impairment in Sjögren's Syndrome via Mitochondrial Dysfunction and TMEM16A Chloride Channel Disruption.
5 affiliations
- 1Department of Oral Medicine, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China.
- 2Department of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Beijing, China.
- 3Central Laboratory, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, NHC Key Laboratory of Digital Stomatology, NMPA Key Laboratory for Dental Materials, Beijing, China.
- 4Department of Oral Pathology, Peking University School and Hospital of Stomatology & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China.
- 5Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions, Chinese Academy of Medical Sciences (2019RU034), Beijing, China.
Abstract
Immune cell-mediated damage to acinar cells plays a central role in Sjögren's syndrome (SS) pathogenesis, with T-cell recruitment being critical in the early stages. In this study, single-cell RNA sequencing was employed to generate transcriptomic profiles of labial gland tissues from SS patients, focusing on GZMK⁺CD8⁺ T cells and their correlation with SS clinical pathology. The role of GZMK⁺CD8⁺ T cells in inducing acinar cell senescence and secretory dysfunction was investigated by co-culturing SMG-C6 acinar cells with GZMK⁺CD8⁺ T cells and recombinant granzyme K. Mechanistically, GZMK induces oxidative stress and mitochondrial dysfunction, thereby promoting senescent phenotypes in acinar cells. Additionally, GZMK-mediated downregulation of TMEM16A contributes to reduced chloride transport and salivary secretion dysfunction. This study provides novel insights into the immune-epithelial crosstalk in SS progression by revealing the relationship between GZMK⁺CD8⁺ T cells and acinar cells. This pathogenic immune-epithelial interaction may offer a promising therapeutic strategy to mitigate SS progression in the early stages and restore salivary secretion in SS patients.
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BibTeX
@article{chai2026gzmkcd8,
title = {{GZMK⁺CD8⁺ T Cells Induce Acinar Cell Senescence and Salivary Secretion Impairment in Sjögren's Syndrome via Mitochondrial Dysfunction and TMEM16A Chloride Channel Disruption.}},
author = {Maosheng Chai and Yufei Xie and Xin Cong and Chong Ding and Pan Wei and Peiru Zhou and Binbin Li and Hong Hua},
journal = {International journal of biological sciences},
year = {2026},
month = oct,
doi = {10.7150/ijbs.134478},
url = {https://europepmc.org/article/MED/42909933},
note = {CC BY},
}
RIS
TY - JOUR
TI - GZMK⁺CD8⁺ T Cells Induce Acinar Cell Senescence and Salivary Secretion Impairment in Sjögren's Syndrome via Mitochondrial Dysfunction and TMEM16A Chloride Channel Disruption.
AU - Maosheng Chai
AU - Yufei Xie
AU - Xin Cong
AU - Chong Ding
AU - Pan Wei
AU - Peiru Zhou
AU - Binbin Li
AU - Hong Hua
PY - 2026
DA - 2026/10/02
JO - International journal of biological sciences
DO - 10.7150/ijbs.134478
UR - https://europepmc.org/article/MED/42909933
AB - Immune cell-mediated damage to acinar cells plays a central role in Sjögren's syndrome (SS) pathogenesis, with T-cell recruitment being critical in the early stages. In this study, single-cell RNA sequencing was employed to generate transcriptomic profiles of labial gland tissues from SS patients, focusing on GZMK⁺CD8⁺ T cells and their correlation with SS clinical pathology. The role of GZMK⁺CD8⁺ T cells in inducing acinar cell senescence and secretory dysfunction was investigated by co-culturing SMG-C6 acinar cells with GZMK⁺CD8⁺ T cells and recombinant granzyme K. Mechanistically, GZMK induces oxidative stress and mitochondrial dysfunction, thereby promoting senescent phenotypes in acinar cells. Additionally, GZMK-mediated downregulation of TMEM16A contributes to reduced chloride transport and salivary secretion dysfunction. This study provides novel insights into the immune-epithelial crosstalk in SS progression by revealing the relationship between GZMK⁺CD8⁺ T cells and acinar cells. This pathogenic immune-epithelial interaction may offer a promising therapeutic strategy to mitigate SS progression in the early stages and restore salivary secretion in SS patients.
SN - 1449-2288
ER -