GALECTIN-1 (GAL1) AND COMPLEX N-GLYCAN COORDINATELY REGULATE SPONTANEOUS DEVELOPMENT OF AUTOIMMUNITY

VERONICA MARTINEZ ALLO; ROSA MORALES; ANGEL DELADOEY; ANASTASIA SECCO; ANTONIO CATALAN PELLET; GABRIEL RABINOVICH; VANESA HAUK; JUAN STUPIRSKI; PRISCILA MARCAIDA; MARTA MAMANI; DIEGO CROCI; MARTA TOSCANO; NICOLAS PINTO; SABRINA GATTO; VIRGINA DURIGAN; ALICIA DOS SANTOS; CLAUDIA PEREZ LEIROS

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Congreso; LXIV REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI); 2016

Galectin-1 (Gal1), an endogenous glycan-bindingprotein, plays a critical role in immune cell homeostasis.Here, we studied the relevance of endogenous Gal1 inthe development of spontaneous autoimmunity. We foundthat aged )aldeficient mice .gals--; ~1-2 y) had increasedtiters of autoantibodies in circulation and morepronounced signs of inflammation and tissue modificationin salivary glands (SG) compared to age-matched WTmice. Moreover, .gals-- SG showed increased numberof infiltrating cells, Yith a higher frequency of C&+ Tcells. As Gal1 binds to N-acetyllactosamine residues incomplex 0glycans, Ye analyzed signs of inflammationin E1,6N-acetylglucosaminyltransferase V-null (Mgat--)mice. Similar to .gals-- mice, aged Mgat-- SG showedincreased number of ducts/mm2 and infiltrating cells, Yithhigher proportion of CD8+, CD4+ and B220+ cells, than WTSG. Seeking for possible mechanisms underlyig this effect,we studied migration and activation factors in CD8+ T cells.We found increased expression of CXCL9 and CXCL10in .gals-- SG and higher percentage of CD8+CXCR3+and CD8+PD1+cells in draining lymph nodes (DLN) andSG when compared to WT mice (P0.05). Moreover,.gals-- DLN had lower frequency of CD11c+ dendriticcells (DCs), and these cells exhibited altered functionality.When co-cultured with CD4+ cells, .gals-- DCs inducedhigher IFN-g and lower IL-10 production (P