Aquaporin gene therapy corrects Sjögren’s syndrome phenotype in mice

Abstract

Primary Sjögren’s syndrome (pSS) is a chronic autoimmune diseasethat is estimated to affect 35 million people worldwide. Currently, noeffective treatments exist for Sjögren’s syndrome, and there is alimited understanding of the physiological mechanisms associatedwith xerostomia and hyposalivation. The present work revealed thataquaporin 5 expression, a water channel critical for salivary glandfluid secretion, is regulated by bone morphogenetic protein 6. In-creased expression of this cytokine is strongly associated with themost common symptom of primary Sjögren’s syndrome, the loss ofsalivary gland function. This finding led us to develop a therapy inthe treatment of Sjögren’s syndrome by increasing the water perme-ability of the gland to restore saliva flow. Our study demonstratesthat the targeted increase of gland permeability not only resulted inthe restoration of secretory gland function but also resolved thehallmark salivary gland inflammation and systemic inflammation as-sociated with disease. Secretory function also increased in the lacri-mal gland, suggesting this local therapy could treat the systemicsymptoms associated with primary Sjögren’ssyndrome.