GZMK+CD8+ T cells Target a Specific Acinar Cell Type in Sjögren’s Disease-Reference-Cited by-同舟云学术

GZMK+CD8+ T cells Target a Specific Acinar Cell Type in Sjögren’s Disease

Published:2023-12-19 Issue: Volume: Page:
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Author:

Warner Blake¹^ORCID,Pranzatelli Thomas²,Perez Paola²^ORCID,Ku Anson³,Matuck Bruno Fernandes⁴,Huynh Khoa,Sakai Shunsuke⁵,Abed Mehdi⁶,Jang Shyh-Ing²,Yamada Eiko⁶,Dominick Kalie⁶,Ahmed Zara⁶,Oliver Amanda⁷^ORCID,Wasikowski Rachael⁸^ORCID,Easter Quinn⁴^ORCID,Magone M. Teresa⁹,Baer Alan¹⁰,Pelayo Eileen¹¹,Khavandgar Zohreh¹⁰,Gupta Sarthak¹²^ORCID,Kleiner David¹³,Lessard Christopher¹⁴^ORCID,Farris A¹⁵^ORCID,Martin Daniel¹⁶^ORCID,Morell Robert¹⁷^ORCID,Zheng Changyu¹⁸,Rachmaninoff Nicholas¹⁹,Maldonado-Ortiz Jose⁶,Qu Xufeng²⁰,Aure Marit²¹,Dezfulian Mohammad²²,Lake Ross²³,Teichmann Sarah⁷^ORCID,Barber Daniel²⁴,Tsoi Lam²⁵,Sowalsky Adam²⁶^ORCID,Tyc Katarzyna²⁷,Gudjonsson Johann²⁸^ORCID,Byrd Kevin²⁹,Johnson Philip¹⁹,Liu Jinze³⁰,Chiorini John¹

Affiliation:

1. National Institute of Dental and Craniofacial Research

2. National Institutes of Health

3. Laboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, National Cancer Institute

4. ADA Science & Research Institute

5. National Institute of Allergy and Infectious Diseases

6. Salivary Disorders Unit, National Institute of Dental and Craniofacial Research

7. Wellcome Sanger Institute

8. University of Michigan-Ann Arbor

9. Consult Services Section, National Eye Institute

10. Sjögren’s Clinical Investigations Team, National Institute of Dental and Craniofacial Research

11. National Institutes of Healh

12. National Institute of Arthritis and Musculoskeletal and Skin Diseases

13. Laboratory of Pathology, Center for Cancer Research, National Cancer Institute

14. Genes & Human Disease Research Program, Oklahoma Medical Research Foundation

15. Oklahoma Medical Research Fd. OMRF

16. NIDCD/NIDCR Genomics and Computational Biology Core

17. Genomics and Computational Biology Core, National Institutes on Deafness and Other Communication Disorders, NIH

18. Genomics and Computational Biology Core, National Institute of Dental and Craniofacial Research,

19. Department of Biology, University of Maryland College Park

20. Massey Cancer Center, Virginia Commonwealth University

21. Matrix and Morphogenesis Section, National Institute of Dental and Craniofacial Research

22. Department of Genetics, Harvard Medical School

23. Laboratory of Genitourinary Cancer Pathogenesis (LCGP) Microscopy Core Facility, Center for Cancer Research, National Cancer Institute

24. T-lymphocyte Biology Section, National Institute of Allergy and Infectious Diseases

25. Medical University of South Carolina

26. National Cancer Institute

27. Department of Biostatistics, Virginia Commonwealth University

28. University of Michigan

29. Lab of Oral & Craniofacial Innovation (LOCI), Department of Innovation & Technology Research, ADA Science & Research Institute

30. Virginia Commonwealth University

Abstract

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.

Publisher

Research Square Platform LLC

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