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Modulation of immune cell reactivity with cis-binding Siglec agonists.

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.

SUBMITTER: Delaveris CS

PROVIDER: S-EPMC7826350 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Modulation of immune cell reactivity with cis-binding Siglec agonists.

Delaveris Corleone S CS Chiu Shannon H SH Riley Nicholas M NM Bertozzi Carolyn R CR

Proceedings of the National Academy of Sciences of the United States of America 20210101 3

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 i ...[more]

PMID: 33431669

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Modulation of immune cell reactivity with cis-binding Siglec-9 agonists

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