Incorporation of a Ligand Peptide for Immune Inhibitory Receptor LAIR-1 on Biomaterial Surfaces Inhibits Macrophage Inflammatory Responses

Abstract

Leukocyte-associated Ig-like receptor-1 (LAIR-1) is an inhibitory receptor broadly expressed on immune cells, with its ligands residing within the extracellular matrix protein collagen. In this study, we modify surfaces with a LAIR-1 ligand peptide (LP), and observe that macrophages cultured on LAIR-1 LP-conjugated surfaces exhibited significantly reduced secretion of inflammatory cytokines in response to proinflammatory stimuli that mimic an injured environment. These downregulated mediators include TNF-α, MIP-1α, MIP-1β, MIP-2, RANTES, and MIG. Knockdown of LAIR-1 using siRNA abrogates this inhibition of cytokine secretion, supporting the specificity of the inhibitory effect to this receptor. These results are the first to demonstrate that integration of LAIR-1 ligands with biomaterials could suppress inflammatory responses.

Graphical abstract