Amsterdam UMC location VUmc, Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam, The Netherlands.
Laboratoire d'Ingénierie des Systèmes Macromoléculaires (LISM), Institut de Microbiologie de la Méditerranée (IMM), CNRS - Aix-Marseille Université, UMR7255, Marseille, France.
Commun Biol. 2021 Dec 20;4(1):1415. doi: 10.1038/s42003-021-02922-4.
Galectins are versatile glycan-binding proteins involved in immunomodulation. Evidence suggests that galectins can control the immunoregulatory function of cytokines and chemokines through direct binding. Here, we report on an inverse mechanism in which chemokines control the immunomodulatory functions of galectins. We show the existence of several specific galectin-chemokine binding pairs, including galectin-1/CXCL4. NMR analyses show that CXCL4 binding induces changes in the galectin-1 carbohydrate binding site. Consequently, CXCL4 alters the glycan-binding affinity and specificity of galectin-1. Regarding immunomodulation, CXCL4 significantly increases the apoptotic activity of galectin-1 on activated CD8 T cells, while no effect is observed in CD4 T cells. The opposite is found for another galectin-chemokine pair, i.e., galectin-9/CCL5. This heterodimer significantly reduces the galectin-9 induced apoptosis of CD4 T cells and not of CD8 T cells. Collectively, the current study describes an immunomodulatory mechanism in which specific galectin-chemokine interactions control the glycan-binding activity and immunoregulatory function of galectins.
半乳糖凝集素是一类多功能的糖结合蛋白，参与免疫调节。有证据表明，半乳糖凝集素可以通过直接结合来控制细胞因子和趋化因子的免疫调节功能。在这里，我们报告了一种相反的机制，即趋化因子控制半乳糖凝集素的免疫调节功能。我们发现了几种特定的半乳糖凝集素-趋化因子结合对，包括半乳糖凝集素-1/CXCL4。NMR 分析表明，CXCL4 结合诱导半乳糖凝集素-1 碳水化合物结合位点的变化。因此，CXCL4 改变了半乳糖凝集素-1 的糖结合亲和力和特异性。关于免疫调节，CXCL4 显著增加了半乳糖凝集素-1 在激活的 CD8 T 细胞上的凋亡活性，而在 CD4 T 细胞中则没有观察到这种作用。另一种半乳糖凝集素-趋化因子对，即半乳糖凝集素-9/CCL5，则相反。这种异二聚体显著降低了半乳糖凝集素-9 诱导的 CD4 T 细胞凋亡，但对 CD8 T 细胞没有影响。总的来说，本研究描述了一种免疫调节机制，其中特定的半乳糖凝集素-趋化因子相互作用控制半乳糖凝集素的糖结合活性和免疫调节功能。
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