Modulation of immune cell reactivity with cis -binding Siglec agonists
- 11 January 2021
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 118 (3)
- https://doi.org/10.1073/pnas.2012408118
Abstract
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.Funding Information
- HHS | NIH | National Cancer Institute (R01CA227942)
- National Science Foundation (DGE-114747)
- HHS | National Institutes of Health (K00CA21245403)
This publication has 74 references indexed in Scilit:
- Ocular Complications After Anti–Vascular Endothelial Growth Factor Therapy in Medicare Patients With Age-Related Macular DegenerationAmerican Journal of Ophthalmology, 2011
- Andromeda: A Peptide Search Engine Integrated into the MaxQuant EnvironmentJournal of Proteome Research, 2011
- The Identification of Markers of Macrophage Differentiation in PMA-Stimulated THP-1 Cells and Monocyte-Derived MacrophagesPLOS ONE, 2010
- Lectins as pattern recognition molecules: The effects of epitope density in innate immunityGlycobiology, 2009
- Sialylated multivalent antigens engage CD22in transand inhibit B cell activationProceedings of the National Academy of Sciences of the United States of America, 2009
- Siglecs and their roles in the immune systemNature Reviews Immunology, 2007
- Highly Efficient Chemoenzymatic Synthesis of Naturally Occurring and Non‐Natural α‐2,6‐Linked Sialosides: A P. damsela α‐2,6‐Sialyltransferase with Extremely Flexible Donor–Substrate SpecificityAngewandte Chemie, 2006
- A cell line model for the differentiation of human dendritic cellsBiochemical and Biophysical Research Communications, 2005
- Alveolar Macrophages as Orchestrators of COPDCOPD: Journal of Chronic Obstructive Pulmonary Disease, 2004
- CD22 as a target of passive immunotherapySeminars in Oncology, 2003