The scavenger receptor MARCO is a ligand for the immune inhibitory receptor LAIR-1 and regulates its function in cis

Akashdip Singh1,2, Saskia V Vijver1,2, Hajar Aglmous-Talibi1,2

  • 1Centre for Translational Immunology, University Medical Centre Utrecht, Utrecht University, Utrecht, Netherlands.

Science Signaling
|December 9, 2025
PubMed

Insights

The scavenger receptor MARCO binds to the inhibitory receptor LAIR-1, modulating immune cell signaling. This interaction enhances immunosuppressive macrophage function by reducing LAIR-1 inhibition.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is an inhibitory receptor recognizing collagens.
  • Macrophage receptor with collagenous structure (MARCO) is a scavenger receptor highly expressed on immunosuppressive macrophages.

Purpose of the Study:

  • To identify MARCO as a ligand for LAIR-1.
  • To investigate the functional consequences of the MARCO-LAIR-1 interaction on immune cell signaling and macrophage function.

Main Methods:

  • Co-immunoprecipitation assays to confirm MARCO-LAIR-1 interaction.
  • In vitro assays using human natural killer (NK) cells and monocyte-derived macrophages.
  • Single-molecule fluorescence microscopy to analyze MARCO-LAIR-1 cis interactions.
  • CRISPR-Cas9 gene editing to knock out MARCO in macrophages.

Main Results:

  • MARCO directly binds to LAIR-1, inducing inhibitory signaling in NK cells.
  • MARCO and LAIR-1 are co-expressed on tumor-associated macrophages and IL-10-stimulated macrophages.
  • MARCO-LAIR-1 interaction reduces LAIR-1 binding and signaling response to collagen.
  • MARCO knockout enhances LAIR-1-mediated inhibition in IL-10-polarized macrophages.

Conclusions:

  • MARCO acts as a novel regulator of LAIR-1 signaling.
  • MARCO induction on immunosuppressive macrophages may enhance their function by alleviating LAIR-1-mediated inhibition.

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