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

VERÓNICA MARTÍNEZ ALLO; VANESA HAUK; NICOLÁS PINTO; ROSA MORALES; JUAN CARLOS STUPIRSKI; SABRINA GATTO; ANGEL DELADOEY; PRISCILA MARCAIDA; VIRGINIA DURIGAN; ANASTASIA SECCO; MARTA MAMANI; ALICIA DOS SANTOS; ANTONIO CATALÁN PELLET; DIEGO CROCI; CLAUDIA PÉREZ LEIROS; GABRIEL RABINOVICH1; MARTA TOSCANO

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Congreso; LXI Reunión Científica de la Sociedad Argentina de Biología (SAIC); LXIV Reunión Anual de la Sociedad Argentina de Inmunología (SAI) y XLVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental (SAFE; 2016

LXI Reunión Científica de la Sociedad Argentina de Biología (SAIC); LXIV Reunión Anual de la Sociedad Argentina de Inmunología (SAI) y XLVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental (SAFE)

Galectin-1 (Gal1), an endogenous glycan-binding protein, plays a critical role in immune cell homeostasis. Here, we studied the relevance of endogenous Gal1 in the development of spontaneous autoimmunity. We found that aged Gal1-deficient mice (Lgals1-/-; ~1-2 y) had increased titers of autoantibodies in circulation and more pronounced signs of inflammation and tissue modification in salivary glands (SG) compared to age-matched WT mice. Moreover, Lgals1-/- SG showed increased number of infiltrating cells, with a higher frequency of CD8+ T cells. As Gal1 binds to N-acetyllactosamine residues in complex N-glycans, we analyzed signs of inflammation in β1,6N-acetylglucosaminyltransferase V-null (Mgat5-/-) mice. Similar to Lgals1-/- mice, aged Mgat5-/- SG showed increased number of ducts/mm2 and infiltrating cells, with higher proportion of CD8+, CD4+ and B220+ cells, than WT SG. Seeking for possible mechanisms underlyig this effect, we studied migration and activation factors in CD8+ T cells. We found increased expression of CXCL9 and CXCL10 in Lgals1-/- SG and higher percentage of CD8+CXCR3+ and CD8+PD1+cells in draining lymph nodes (DLN) and SG when compared to WT mice (P