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Regulatory T cell activation triggers specific changes in glycosylation associated with Siglec-1-dependent inflammatory responses
bioRxiv - Immunology Pub Date : 2020-07-30 , DOI: 10.1101/2020.07.29.226399
Gang Wu , Gavuthami Murugesan , Manjula Nagala , Alex McCraw , Stuart M. Haslam , Anne Dell , Paul R. Crocker

Siglec-1 is a macrophage lectin-like receptor that mediates sialic acid-dependent cellular interactions. It was shown previously to promote inflammation in autoimmune disease through suppressing the expansion of regulatory T cells (Tregs). We have investigated the molecular basis for Siglec-1 binding to these cells using in vitro-induced Tregs. Siglec-1 binding was strongly upregulated on activated cells, but lost under resting conditions. Glycosylation changes that affect Siglec 1 binding were studied by comparing activated and resting Tregs using RNA-Seq, glycomics, proteomics and binding of selected antibodies and lectins. A proximity labelling and proteomics strategy identified 49 glycoproteins expressed by activated Tregs that may function as Siglec-1 counter-receptors. These represent ~5% of the total membrane protein pool and were mainly related to T cell activation and proliferation. We demonstrate that several of these counter-receptors are upregulated following activation of Tregs and provide initial evidence that their altered glycosylation may also be important for Siglec-1 binding.

中文翻译:

调节性T细胞活化触发与Siglec-1依赖性炎症反应相关的糖基化的特定变化

Siglec-1是一种巨噬细胞凝集素样受体,可介导唾液酸依赖性细胞相互作用。先前已证明可通过抑制调节性T细胞(Tregs)的扩增来促进自身免疫性疾病的炎症。我们已经使用体外诱导的Tregs研究了Siglec-1与这些细胞结合的分子基础。Siglec-1结合在活化细胞上强烈上调,但在静止条件下丧失。通过使用RNA-Seq,糖组学,蛋白质组学和所选抗体与凝集素的结合,比较活化的Treg和静止的Treg,研究了影响Siglec 1结合的糖基化变化。邻近标记和蛋白质组学策略鉴定了由活化的Tregs表达的49种糖蛋白,这些糖蛋白可能起着Siglec-1反受体的作用。这些占总膜蛋白池的约5%,并且主要与T细胞的活化和增殖有关。我们证明了这些反受体中的几个在激活Treg后被上调,并提供了初步的证据表明它们改变的糖基化作用对于Siglec-1结合也可能很重要。
更新日期:2020-07-30
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