Journal article
T cell exosome–derived miR-142-3p impairs glandular cell function in Sjögren’s syndrome
JCI insight, v 5(9)
07 May 2020
PMID: 32376798
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Sjögren’s syndrome (SS) is a systemic autoimmune disease that mainly affects exocrine salivary and lacrimal glands. Local inflammation in the glands is thought to trigger glandular dysfunction and symptoms of dryness. However, the mechanisms underlying these processes are incompletely understood. Our work suggests T cell exosome–derived miR-142-3p as a pathogenic driver of immunopathology in SS. We first document miR-142-3p expression in the salivary glands of patients with SS, both in epithelial gland cells and within T cells of the inflammatory infiltrate, but not in healthy volunteers. Next, we show that activated T cells secreted exosomes containing miR-142-3p, which transferred into glandular cells. Finally, we uncover a functional role of miR-142-3p–containing exosomes in glandular cell dysfunction. We find that miR-142-3p targets key elements of intracellular Ca
2+
signaling and cAMP production — sarco(endo)plasmic reticulum Ca
2+
ATPase 2b (SERCA2B), ryanodine receptor 2 (RyR2), and adenylate cyclase 9 (AC9) — leading to restricted cAMP production, altered calcium signaling, and decreased protein production from salivary gland cells. Our work provides evidence for a functional role of the miR-142-3p in SS pathogenesis and promotes the concept that T cell activation may directly impair epithelial cell function through secretion of miRNA-containing exosomes.
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Details
- Title
- T cell exosome–derived miR-142-3p impairs glandular cell function in Sjögren’s syndrome
- Creators
- Juan Cortes-Troncoso - University of ChileShyh-Ing Jang - University of ChilePaola Perez - National Institute of Dental and Craniofacial ResearchJorge Hidalgo - University of ChileTomoko Ikeuchi - University of ChileTeresa Greenwell-Wild - University of ChileBlake M. Warner - University of ChileNiki M. Moutsopoulos - University of ChileIlias Alevizos - University of Chile
- Publication Details
- JCI insight, v 5(9)
- Publisher
- American Society for Clinical Investigation
- Grant note
- Intram / NIH/NIDCR Intramural / NIDCR
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; Drexel University
- Web of Science ID
- WOS:000531472400007
- Scopus ID
- 2-s2.0-85084410966
- Other Identifier
- 991019415772004721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Medicine, Research & Experimental