Monocytes from Sjögren syndrome patients display increased VPAC2 expression and impaired apoptotic cell phagocytosis.

VANESA HAUK; LAURA FRACCAROLI; ESTEBAN GRASSO; ALICIA EIMON; ROSANNA RAMHORST; OSVALDO HUBSCHER; CLAUDIA PEREZ LEIROS

CLINICAL AND EXPERIMENTAL IMMUNOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2014 vol. 177 p. 662 - 670

0009-9104

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 aberrant epithelial cell apoptosis and immune homeostasis loss in the glands as triggering factors for the autoimmune response. Vasoactive intestinal peptide promotes potent anti-inflammatory effects in several inflammatory and autoimmune disease models including the non obese diabetic (NOD) mouse model of SS. On the knowledge that VIP modulates monocyte function through VPAC receptors and that immune homeostasis maintenance strongly depends on a rapid and immunosuppressant apoptotic cell clearance by monocytes/macrophages, here we explored VPAC expression on monocytes from primary SS (pSS) patients and the ability of VIP to modulate apoptotic cell phagocytic function and cytokine profile. Monocytes isolated from individual pSS patients showed an increased expression of VPAC2 subtype of VIP receptors, absent in monocytes from control subjects, with no changes in VPAC1 expression. VPAC2 receptor expression could be further induced with LPS in pSS monocytes and VIP inhibited the effect. Moreover, monocytes from pSS patients showed an impaired phagocytosis of apoptotic epithelial cells as evidenced by reduced engulfment ability and the failure to promote an immunosuppressant cytokine profile. However, VIP neither modulated monocyte/macrophage phagocytic function nor did it reverse their inflammatory profile. We conclude that monocytes from pSS patients express high levels of VPAC2 and display a deficient clearance of apoptotic cells that is not modulated by VIP.