Modulation of immune cell reactivity with cis-binding Siglec agonists.
Corleone S DelaverisShannon H ChiuNicholas M RileyCarolyn R BertozziPublished in: Proceedings of the National Academy of Sciences of the United States of America (2021)
Inflammatory pathologies caused by phagocytes lead to numerous debilitating conditions, including chronic pain and blindness due to age-related macular degeneration. Many members of the sialic acid-binding immunoglobulin-like lectin (Siglec) family are immunoinhibitory receptors whose agonism is an attractive approach for antiinflammatory therapy. Here, we show that synthetic lipid-conjugated glycopolypeptides can insert into cell membranes and engage Siglec receptors in cis, leading to inhibitory signaling. Specifically, we construct a cis-binding agonist of Siglec-9 and show that it modulates mitogen-activated protein kinase (MAPK) signaling in reporter cell lines, immortalized macrophage and microglial cell lines, and primary human macrophages. Thus, these cis-binding agonists of Siglecs present a method for therapeutic suppression of immune cell reactivity.
Keyphrases
- chronic pain
- age related macular degeneration
- dna binding
- binding protein
- endothelial cells
- oxidative stress
- single cell
- adipose tissue
- crispr cas
- cell proliferation
- lipopolysaccharide induced
- transcription factor
- spinal cord injury
- pain management
- tyrosine kinase
- mesenchymal stem cells
- protein kinase
- pi k akt
- cell surface