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@article{Wu:2021:10.12688/wellcomeopenres.16834.1,
author = {Wu, G and Murugesan, G and Nagala, M and McCraw, A and Haslam, SM and Dell, A and Crocker, PR},
doi = {10.12688/wellcomeopenres.16834.1},
journal = {Wellcome Open Research},
title = {Activation of regulatory T cells triggers specific changes in glycosylation associated with Siglec-1-dependent inflammatory responses [version 1; peer review: 2 approved]},
url = {http://dx.doi.org/10.12688/wellcomeopenres.16834.1},
volume = {6},
year = {2021}
}

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TY  - JOUR
AB  - Background: Siglec-1 is a macrophage lectin-like receptor that mediates sialic acid-dependent cellular interactions. Its upregulation on macrophages in autoimmune disease was shown previously to promote inflammation through suppressing the expansion of regulatory T cells (Tregs). Here we investigate the molecular basis for Siglec-1 binding to Tregs using in vitro-induced cells as a model system. Methods: Glycosylation changes that affect Siglec1 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 was used to identify Siglec-1 counter-receptors expressed on activated Tregs. Results: Siglec-1 binding was strongly upregulated on activated Tregs, but lost under resting conditions. Glycomics revealed changes in N-glycans and glycolipids following Treg activation and we observed changes in expression of multiple 'glycogenes' that could lead to the observed increase in Siglec-1 binding. Proximity labelling of intact, living cells 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 were upregulated following activation of Tregs and provide initial evidence that their altered glycosylation may also be important for Siglec-1 binding. Conclusions: We provide the first comprehensive analysis of glycan changes that occur in activated Tregs, leading to recognition by the macrophage lectin, Siglec-1 and suppression of Treg expansion. We furthermore provide insights into glycoprotein counter-receptors for Siglec-1 expressed by activated Tregs that are likely to be important for suppressing Treg expansion.
AU  - Wu,G
AU  - Murugesan,G
AU  - Nagala,M
AU  - McCraw,A
AU  - Haslam,SM
AU  - Dell,A
AU  - Crocker,PR
DO  - 10.12688/wellcomeopenres.16834.1
PY  - 2021///
SN  - 2398-502X
TI  - Activation of regulatory T cells triggers specific changes in glycosylation associated with Siglec-1-dependent inflammatory responses [version 1; peer review: 2 approved]
T2  - Wellcome Open Research
UR  - http://dx.doi.org/10.12688/wellcomeopenres.16834.1
UR  - https://www.ncbi.nlm.nih.gov/pubmed/35224210
UR  - http://hdl.handle.net/10044/1/95368
VL  - 6
ER  -

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