Relevance of the galectin-1 (Gal1)-N-glycan axis in the development of spontaneous sialadenitis

V MARTINEZ ALLO; V HAUK; R MORALES; E MARONNA; D CROCI; J STUPIRSKI; J CERLIANI; N PINTO; C PÉREZ LEIROS; G RABINOVICH; M TOSCANO

Buenos Aires

Simposio; Primer Simposio Argentino de Glicobiología Glycoar2014; 2014

FIL, IBYME, IFYBINE

Gal1, an endogenous β-galactoside-binding protein, plays a critical role in immune cell homeostasis and administration of rGal1 can suppress the clinical signs of autoimmunity and chronic inflammation. However, the role of endogenous Gal1 in the development of spontaneous autoimmunity has not yet been studied. Thus, we evaluated organs of aged Gal1 deficient mice (Lgals1-/-) and WT mice and  found that salivary glands of Lgals1-/- mice (~20 month) have increased weight and signs of inflammation compared to WT mice (P<0.05). In addition Lgals1-/-mice have increased number of infiltrating cells characterized by an increased proportion of CD8+ T cells. We also found lower frequency of CD8+ T lymphocytes and higher percentage of CD4+ T cells in spleens with increased T cell proliferation in Lgals1-/-versus WT mice. Since Gal1 binds to N-acetyllactosamine residues in N-glycans, we next analyzed the signs of inflammation in aged Mgat5-deficient mice (Mgat5-/-; ~9 month). We found that, similar to aged Lgals1-/-mice, salivary glands from Mgat5-/- mice have increased weight and increased number of infiltrating cells when compared to WT mice. In comparison to WT mice, the cellular composition of the infiltrates showed higher proportion of CD8+, CD4+ and B220+ cells in Mgat5-/- salivary glands.These results suggest that Gal1 and its ligands may play critical roles in the control of salivary glands homeostasis, modulation of immune responses and development of autoimmunity.