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Sialic acid–binding immunoglobulin-like lectins (Siglecs) detect self-associated molecular patterns to regulate immune responses

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Abstract

The mammalian immune system evolved to tightly regulate the elimination of pathogenic microbes and neoplastic transformed cells while tolerating our own healthy cells. Here, we summarize experimental evidence for the role of Siglecs—in particular CD33-related Siglecs—as self-receptors and their sialoglycan ligands in regulating this balance between recognition of self and non-self. Sialoglycans are found in the glycocalyx and extracellular fluids and matrices of all mammalian cells and can be considered as self-associated molecular patterns (SAMPs). We also provide an overview of the known interactions of Siglec receptors and sialoglycan-SAMPs. Manipulation of the Siglec-SAMP axis offers new therapeutic opportunities for the treatment of inflammatory conditions, autoimmune diseases and also cancer immunotherapy.

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Acknowledgements

Figure 2 was made with graphs provided by SMART (Servier Medical Art).

Funding

This work was supported by funding to HL from the Goldschmidt-Jacobson Foundation, the Swiss National Science Foundation (Grant 310030_184720 to HL), the Schoenemakers Foundation (to HL), and to NIH Grant (GM32373 AV).

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  1. Laboratory for Cancer Immunotherapy, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland

    Heinz Läubli

  2. Department of Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA, 92093-0687, USA

    Ajit Varki

  3. Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA, 92093-0687, USA

    Ajit Varki

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  1. Heinz Läubli
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HL and AV wrote the manuscript.

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HL received travel grants and consultant fees from Bristol-Myers Squibb (BMS), Merck, Sharp and Dohme (MSD), and Roche. HL received research support from BMS and Palleon Pharmaceuticals.

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Läubli, H., Varki, A. Sialic acid–binding immunoglobulin-like lectins (Siglecs) detect self-associated molecular patterns to regulate immune responses. Cell. Mol. Life Sci. 77, 593–605 (2020). https://doi.org/10.1007/s00018-019-03288-x

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