Targeting the Ca2+ Sensor STIM1 by Exosomal Transfer of Ebv-miR-BART13-3p is Associated with Sjögren's Syndrome
Alessia Gallo,
Shyh-Ing Jang,
Hwei Ling Ong,
Paola Perez,
Mayank Tandon,
Indu Ambudkar,
Gabor Illei,
Ilias Alevizos
Affiliations
Alessia Gallo
Sjögren's Syndrome and Salivary Gland Dysfunction Unit, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, USA
Shyh-Ing Jang
Sjögren's Syndrome and Salivary Gland Dysfunction Unit, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, USA
Hwei Ling Ong
Secretory Physiology Section, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, USA
Paola Perez
Sjögren's Syndrome and Salivary Gland Dysfunction Unit, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, USA
Mayank Tandon
Sjögren's Syndrome and Salivary Gland Dysfunction Unit, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, USA
Indu Ambudkar
Secretory Physiology Section, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, USA
Gabor Illei
Sjögren's Syndrome and Salivary Gland Dysfunction Unit, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, USA
Ilias Alevizos
Sjögren's Syndrome and Salivary Gland Dysfunction Unit, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, USA
Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease that is associated with inflammation and dysfunction of salivary and lacrimal glands. The molecular mechanism(s) underlying this exocrinopathy is not known, although the syndrome has been associated with viruses, such as the Epstein Barr Virus (EBV). We report herein that an EBV-specific microRNA (ebv-miR-BART13-3p) is significantly elevated in salivary glands (SGs) of pSS patients and we show that it targets stromal interacting molecule 1 (STIM1), a primary regulator of the store-operated Ca2+ entry (SOCE) pathway that is essential for SG function, leading to loss of SOCE and Ca2+-dependent activation of NFAT. Although EBV typically infects B cells and not salivary epithelial cells, ebv-miR-BART13-3p is present in both cell types in pSS SGs. Importantly, we further demonstrate that ebv-miR-BART13-3p can be transferred from B cells to salivary epithelial cells through exosomes and it recapitulates its functional effects on calcium signaling in a model system.
