Impact of galectin-1 deciency in the development of spontaneous sialadenitis

VERONICA MARTINES ALLO; VANESA HAUK; JUAN CERLIANI; TOMAS DALOTTO; DIEGO CROCI; SANTIAGO MENDEZ HUERGO; ROSA MORALES; JUAN STUPIRSKI; CLAUDIA PEREZ LEIROS; GABRIEL RABINOVICH; MARTA TOSCANO

Cordoba

Congreso; Reunion Anual de la Sociedad Argentina de Inmunologia; 2013

SAI

During the past years, galectins, a family of β-galactosides-binding proteins, have been implicated in several biological processes as regulators of the immune system. Particularly, galectin-1 (Gal1) has been shown to play a critical role in the homeostasis of the immune response. Recombinant Gal1 suppresses the clinical manifestations in dierent experimental models of chronic inammation and autoimmunity as collagen II induced arthritis and experimental autoimmune uveitis, among others. However, the role of endogenous Gal1 in the development of spontaneous autoimmunity has not been studied. For this purpose, we evaluated organs and blood serum of aged Gal1 decient mice (Lgals1-/-) and WT mice. We found that salivary glands of aged Lgals1-/- mice (~20 mo) have increased weight and signs of inammation as compared to age and sex-matched WT mice. The histological analyses reveal that Lgals1-/- mice have increased inammatory score than WT mice. Using ow cytometry, we found increased number of inltrating cells in Lgals1-/- mice. When we analyze the cellular composition of the inltrates we observed an increased proportion of CD8+ cells in salivary glands in comparison to WT mice . At systemic level, a lower proportion of CD8+ lymphocytes and higher proportion of CD4+ cells was observed, with more proliferation of splenocytes in Lgals1-/- mice versus WT mice. Concurrently, we analyzed the expression of Gal1 in a model of spontaneous sialadenitis in NOD mice. We observed diminish Gal1 mRNA in submaxilar glands of NOD mice in parallel to diminished production of saliva. In addition, we observed a ductal localization of Gal1 by immunohistochemistry analysis. At systemic level, we found an increase in serum Gal1 of 26 weeks old NOD mice with respect to 19-22 weeks old NOD mice. These results suggest that Gal1 plays a critical role in the regulation of the salivary glands homeostasis, the modulation of the immune response and the development of autoimmunity.