ROLE OF VIP IN IMMUNE HOMEOSTASIS MAINTENANCE IN SALIVARY GLANDS: RELEVANCE TO SJÖGREN'S SYNDROME PATHOGENESIS

PEREZ LEIROS C

Uchisar

Congreso; 12th International Symposium on VIP, PACAP and Related; 2015

VIP PACAP and Related Peptides Symposia

Sjögren?s syndrome (SS) is a chronic autoimmune disease characterized by salivary and lacrimal gland dysfunction. Clinical observations and results from animal models of SS support the role of epithelial cell aberrant apoptosis and enhanced expression of pro-inflammatory markers as triggering factors for the autoimmune response. Vasoactive intestinal peptide (VIP) is secretagogue and trophic in salivary glands. It promotes anti-inflammatory effects in autoimmune disease models including the non obese diabetic (NOD) mouse model of SS. On this basis, and considering that tissue homeostasis maintenance strongly depends on a rapid and immunosuppressant apoptotic cell clearance by monocytes and macrophages, we explored the ability of VIP to modulate apoptotic cell phagocytosis by monocytes isolated from primary SS (pSS) patients. Its effect on early events of the interaction between salivary gland epithelial cells and peripheral blood mononuclear cells (PBMC) from pSS patients was also tested. By means of co-cultures of PBMC or purified monocytes from individual pSS patients or control subjects with a human salivary gland epithelial cell line (HSG), we observed that monocytes from pSS patients express VPAC2, absent in control monocytes, and display an impaired phagocytosis of apoptotic epithelial cells evidenced by reduced engulfment ability and the failure to promote an immunosuppressant cytokine profile that were not reversed by VIP. In addition, the interaction of PBMC with gland epithelial cells induced IL-12 synthesis in pSS but not in control monocytes, whereas epithelial cells showed higher expression of pro-inflammatory signals and reduced migration capacity. VIP only partially modulated pro-inflammatory signals in both cell types. These results support that an impaired VIP regulation of early pro-inflammatory events in the interaction of epithelial and immune cells might have a role in pSS pathogenesis.AcknowledgementThis study was supported by CONICET and University of Buenos Aires grants PIP 602/12 and UBACyT 20020130100040BA.