CONICET | Buscador de Institutos y Recursos Humanos

We have recently shown that Th1-, Th2-or Th17-promoting stimuli can regulate the glycosylation pattern of T-helper cells and modulate their susceptibility to Gal1, a member of the galectin family with anti-inflammatory activity. While Th1- and Th17-differentiated cells express the repertoire of glycans required for Gal1 function, Th2 cells are protected through α2,6 sialylation of surface glycoproteins. The aim of the present study is to analyze the influence of Gal1 in the physiology of Treg cells and its implications for the development of spontaneous autoimmune pathology. Similar to Th2 cells, CD4+CD25+FoxP3+ Treg cells displayed increased levels of α2,6 sialic acid and were resistant to Gal1-induced apoptosis. However, CD4+ T cells from Gal1-deficient (Lgals1/) mice showed diminished capacity to differentiate into Foxp3+ Treg cells in vitro and decreased capacity to suppress autoimmune responses in vivo (P<0.05). Consistent with the anti-inflammatory activity of Gal1, aged Lgals1/ mice spontaneously developed symptoms associated with autoimmune diseases such as Sjögren´s-like sialadenitis [Lgals-1-/-:1,22±0.38 vs. WT:0.46±0.19 (inflammatory foci/4mm2)] and elevated levels of anti-dsDNA autoantibodies [Lgals-1-/-:37,6±13,2 vs. WT:14,6 ± 9,2 (103U/ml)]. Collectively, these findings suggest that Gal1 plays a crucial role in maintaining T cell homeostasis and provide new insights into the pathogenesis of autoimmune diseases.