Neuroimmune modulation of secretory function in an experimental model of Sjögren’s Syndrome

HAUK V; CALAFAT M; LAROCCA L; RAMHORST R; PEREZ LEIROS C

Simposio; I French Argentine Immunology Congress; 2010

Sjögren´s syndrome is a chronic autoimmune disorder characterized by a progressive loss of exocrine secretion. The pathogenic mechanisms of disease are presently unknown and the active involvement of epithelial acinar cells producing inflammatory mediators in the induction and perpetuation of the inflammatory response supports its characterization as an autoimmune exocrinopathy. The hypothesis of an impaired balance of neuroimmune interactions in the target organ at the onset of the disease can be approached in the non-obese diabetic (NOD) mouse model of SS. At the pre-diabetic stage, NOD mice have the unique characteristic of developing a deep secretory loss with mild infiltration of the glands consistent with a structural-dysfunctional aetiology. In keeping with a defect in salivary gland homeostasis as initial trigger of the autoimmune exocrinopathy, an enhanced apoptosis of acinar cells and reduced salivary secretion and signaling upon vasoactive intestinal peptide (VIP) stimulation was observed. VIP is a neuro- and immunopeptide that promotes exocrine secretion, contributes to vasodilation in exocrine glands and induces anti-inflammatory effects through its action on macrophages. On this basis, we are currently exploring the role of apoptotic secretory epithelium as a pro-inflammatory triggering factor of exocrine dysfunction in the NOD model of Sjogren´s syndrome and the modulatory effect of VIP on the dialogue of acinar cells and macrophages.