Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Santiago de Compostela, A Coruña, Spain.
Cell Immunol. 2011;271(2):319-28. doi: 10.1016/j.cellimm.2011.07.010. Epub 2011 Jul 23.
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.
半乳糖凝集素是一组β-半乳糖苷结合的哺乳动物凝集素，通过促进 T 细胞耐受、削弱 Th1 和 Th17 反应以及抑制自身免疫炎症，在调节免疫反应中发挥重要作用。然而，不同 T 辅助（Th）亚群在人类 1 型糖尿病（T1D）背景下这些分子的合成尚未得到研究。我们的结果表明，与 Th1 极化的淋巴细胞相比，Th17 极化条件诱导更高水平的半乳糖凝集素-1 合成。在人类糖尿病的背景下，与健康供体相比，T1D 患者的外周血单核细胞（PBMC）无论是未经刺激还是刺激后，体外分泌的半乳糖凝集素-1 明显减少。在这种自身免疫性疾病中观察到的半乳糖凝集素-1 合成减少发生在主要的促炎细胞因子环境中，主要是由于单核细胞的合成减少。令人惊讶的是，与健康供体相比，来自这些患者的 CD4(+) T 辅助细胞分泌的半乳糖凝集素-1 水平相似，可能是由 Th17 细胞因子介导的。总之，T1D 患者的 CD4(+) T 辅助淋巴细胞产生正常水平的免疫调节剂半乳糖凝集素-1，但单核细胞对半乳糖凝集素-1 合成的减少有助于维持偏向促炎的反应。
