Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.29.226399v1?rss=1 Authors: Wu, G., Murugesan, G., Nagala, M., McCraw, A., Haslam, S. M., Dell, A., Crocker, P. R. Abstract: 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. Copy rights belong to original authors. Visit the link for more info