TY - JOUR
T1 - The scavenger receptor MARCO is a ligand for the immune inhibitory receptor LAIR-1 and regulates its function in cis
AU - Singh, Akashdip
AU - Vijver, Saskia V.
AU - Aglmous-Talibi, Hajar
AU - Jukic, Nebojsa
AU - Chen, Peirong
AU - Crawley, Suzanne
AU - Mondal, Kalyani
AU - Zhou, Jing
AU - Niederauer, Christian
AU - Matharu, Zimple
AU - Li, Betty
AU - Fan, Bin
AU - van der Vlist, Michiel
AU - Kaplan, Daniel D.
AU - Rivera, Lee B.
AU - Sissons, James
AU - Sitrin, Jonathan
AU - Ganzinger, Kristina A.
AU - Inês Pascoal Ramos, M.
AU - Meyaard, Linde
N1 - Publisher Copyright:
© 2025 The Authors, some rights reserved;.
PY - 2025/12/9
Y1 - 2025/12/9
N2 - LAIR-1 is an inhibitory receptor on immune cells that recognizes collagens and collagen domain-containing proteins. The high abundance of both LAIR-1 and its ligands suggests tight regulation of this interaction. MARCO is a scavenger receptor with a collagen-like domain that is highly expressed on immunosuppressive macrophages. Here, we identified MARCO as a ligand for LAIR-1. MARCO interacted with LAIR-1 in trans and induced inhibitory signaling by LAIR-1 in human natural killer (NK) cells. MARCO and LAIR-1 were coexpressed by human macrophages in tumors and after stimulation of monocyte-derived macrophages with the cytokine interleukin-10 (IL-10) in vitro. Single-molecule fluorescence microscopy demonstrated that MARCO and LAIR-1 interacted in cis on THP-1 macrophages. Whereas the interaction did not affect the scavenger function of MARCO on human macrophages, it reduced both LAIR-1 binding and the LAIR-1 signaling response to collagen. LAIR-1-mediated inhibitory function was increased after CRISPR-Cas9-mediated knockout of MARCO in IL-10-polarized primary human monocyte-derived macrophages. Our results identify MARCO as a regulator of LAIR-1 signaling and suggest that the induction of MARCO on immunosuppressive macrophages could enhance their function by releasing LAIR-1-mediated inhibition.
AB - LAIR-1 is an inhibitory receptor on immune cells that recognizes collagens and collagen domain-containing proteins. The high abundance of both LAIR-1 and its ligands suggests tight regulation of this interaction. MARCO is a scavenger receptor with a collagen-like domain that is highly expressed on immunosuppressive macrophages. Here, we identified MARCO as a ligand for LAIR-1. MARCO interacted with LAIR-1 in trans and induced inhibitory signaling by LAIR-1 in human natural killer (NK) cells. MARCO and LAIR-1 were coexpressed by human macrophages in tumors and after stimulation of monocyte-derived macrophages with the cytokine interleukin-10 (IL-10) in vitro. Single-molecule fluorescence microscopy demonstrated that MARCO and LAIR-1 interacted in cis on THP-1 macrophages. Whereas the interaction did not affect the scavenger function of MARCO on human macrophages, it reduced both LAIR-1 binding and the LAIR-1 signaling response to collagen. LAIR-1-mediated inhibitory function was increased after CRISPR-Cas9-mediated knockout of MARCO in IL-10-polarized primary human monocyte-derived macrophages. Our results identify MARCO as a regulator of LAIR-1 signaling and suggest that the induction of MARCO on immunosuppressive macrophages could enhance their function by releasing LAIR-1-mediated inhibition.
UR - https://www.scopus.com/pages/publications/105024385728
U2 - 10.1126/scisignal.ado2768
DO - 10.1126/scisignal.ado2768
M3 - Article
C2 - 41364749
AN - SCOPUS:105024385728
SN - 1937-9145
VL - 18
JO - Science signaling
JF - Science signaling
IS - 916
M1 - eado2768
ER -