| First Author | Teos LY | Year | 2015 |
| Journal | Sci Rep | Volume | 5 |
| Pages | 13953 | PubMed ID | 26365984 |
| Mgi Jnum | J:269238 | Mgi Id | MGI:6215362 |
| Doi | 10.1038/srep13953 | Citation | Teos LY, et al. (2015) IP3R deficit underlies loss of salivary fluid secretion in Sjogren's Syndrome. Sci Rep 5:13953 |
| abstractText | The autoimmune exocrinopathy, Sjogren's syndrome (SS), is associated with secretory defects in patients, including individuals with mild lymphocytic infiltration and minimal glandular damage. The mechanism(s) underlying the secretory dysfunction is not known. We have used minor salivary gland biopsies from SS patients and healthy individuals to assess acinar cell function in morphologically intact glandular areas. We report that agonist-regulated intracellular Ca(2+) release, critically required for Ca(2+) entry and fluid secretion, is defective in acini from SS patients. Importantly, these acini displayed reduction in IP3R2 and IP3R3, but not AQP5 or STIM1. Similar decreases in IP3R and carbachol (CCh)-stimulated [Ca(2+)]i elevation were detected in acinar cells from lymphotoxin-alpha (LTalpha) transgenic (TG) mice, a model for (SS). Treatment of salivary glands from healthy individuals with LT alpha, a cytokine linked to disease progression in SS and IL14alpha mice, reduced Ca(2+) signaling. Together, our findings reveal novel IP3R deficits in acinar cells that underlie secretory dysfunction in SS patients. |
