Galectin-1 synthesis in type 1 diabetes by different immune cell types: reduced synthesis by monocytes and Th1 cells

Abstract

Galectins are a group of β-galactoside-binding mammalian lectins that play important roles in the regulation of the immune response by promoting T cell tolerance, blunting Th1 and Th17 responses and suppressing autoimmune inflammation. However, the synthesis of these molecules by different T helper (Th) subsets and in the context of human type 1 diabetes (T1D) has not yet been studied. Our results show that Th17 polarising conditions induce the synthesis of higher levels of galectin-1 compared to Th1-polarised lymphocytes. In the context of human diabetes, peripheral blood mononuclear cells (PBMCs) from T1D patients, either unstimulated or after stimulation, secreted significantly lower amounts of galectin-1 in vitro compared to healthy donors. The reduced galectin-1 synthesis observed in this autoimmune disease occurs in a dominant pro-inflammatory cytokine milieu and it is mainly due to the lower synthesis by monocytes. Surprisingly, CD4(+) T helper cells from these patients secreted similar levels of galectin-1 compared to healthy donors, probably mediated by Th17 cytokines. In conclusion, CD4(+) T helper lymphocytes from T1D patients produce normal levels of the immunoregulator galectin-1 but its reduced synthesis by monocytes helps to maintain a skewed pro-inflammatory response.