CD160 is an inducible endothelial checkpoint that suppresses sprouting angiogenesis through LRP1-dependent autophagy
- 1Universite de Reims Champagne-Ardenne, UMR CNRS/URCA 7369 MEDyC, Reims, France
Abstract
Pathological angiogenesis is a hallmark of cancer and other chronic diseases, yet therapeutic strategies remain largely focused on blocking pro-angiogenic signals rather than restoring endogenous mechanisms that restrain endothelial sprouting. The identification of endothelial checkpoints capable of limiting pathological vessel growth therefore remains an important unmet need. CD160 is a glycosylphosphatidylinositol-anchored immunoglobulin-superfamily receptor of cytotoxic lymphocytes and an inhibitory checkpoint receptor on CD4 T cells. It is also present on endothelium and has been targeted therapeutically. Here, we identify CD160 as an inducible endothelial checkpoint that emerges in response to pro-angiogenic cues and limits pathological angiogenesis. CD160 is absent in resting endothelium. It is induced by basic fibroblast growth factor (bFGF) and most strongly by combining VEGF-A and bFGF, and it is detected in the sprouting region of ex vivo mouse aortic rings. Targeting of CD160 using monoclonal antibody reduces tubulogenesis, scratch closure and aortic-ring sprouting, and softens the cell cortex, while viability and membrane integrity remain intact. Mechanistically, CD160 associates with the endocytic receptor LRP1 as demonstrated by proximity ligation assay, lipid-raft co-immunoprecipitation and super-resolution fluorescence microscopy. Both receptors appear in a common complex, and two independent computational methods converge on the first ligand-binding cluster of LRP1 as the interface. Silencing CD160 or LRP1 abolishes the anti-angiogenic response mediated by the antibody. Under a chloroquine clamp, engagement raises autophagic flux in a CD160- and LRP1-dependent manner, and lysosomal or LDL-receptor-family blockade removes the anti-sprouting effect. CD160 therefore acts as an inducible endothelial checkpoint that suppresses sprouting through autophagic flux. Thus, CD160 represents an inducible endothelial checkpoint that is activated in a pro-angiogenic environment, and targeting CD160 restrains pathological angiogensis.
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BibTeX
@misc{aziz2026cd160,
title = {{CD160 is an inducible endothelial checkpoint that suppresses sprouting angiogenesis through LRP1-dependent autophagy}},
author = {A.-I. Aziz and M. Mocquery-Corre and A. Berquand and J. Thevenard-Devy and A. Martins and C. Hachet and S. Potteaux and Y. Merrouche and R. El Fatimy and L. Duca and A. Bensussan and S. Ben Mkaddem and J. Devy},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.19.760050},
url = {https://www.biorxiv.org/content/10.64898/2026.10.19.760050v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - CD160 is an inducible endothelial checkpoint that suppresses sprouting angiogenesis through LRP1-dependent autophagy
AU - A.-I. Aziz
AU - M. Mocquery-Corre
AU - A. Berquand
AU - J. Thevenard-Devy
AU - A. Martins
AU - C. Hachet
AU - S. Potteaux
AU - Y. Merrouche
AU - R. El Fatimy
AU - L. Duca
AU - A. Bensussan
AU - S. Ben Mkaddem
AU - J. Devy
PY - 2026
DA - 2026/10/19
PB - bioRxiv
DO - 10.64898/2026.10.19.760050
UR - https://www.biorxiv.org/content/10.64898/2026.10.19.760050v1
AB - Pathological angiogenesis is a hallmark of cancer and other chronic diseases, yet therapeutic strategies remain largely focused on blocking pro-angiogenic signals rather than restoring endogenous mechanisms that restrain endothelial sprouting. The identification of endothelial checkpoints capable of limiting pathological vessel growth therefore remains an important unmet need. CD160 is a glycosylphosphatidylinositol-anchored immunoglobulin-superfamily receptor of cytotoxic lymphocytes and an inhibitory checkpoint receptor on CD4 T cells. It is also present on endothelium and has been targeted therapeutically. Here, we identify CD160 as an inducible endothelial checkpoint that emerges in response to pro-angiogenic cues and limits pathological angiogenesis. CD160 is absent in resting endothelium. It is induced by basic fibroblast growth factor (bFGF) and most strongly by combining VEGF-A and bFGF, and it is detected in the sprouting region of ex vivo mouse aortic rings. Targeting of CD160 using monoclonal antibody reduces tubulogenesis, scratch closure and aortic-ring sprouting, and softens the cell cortex, while viability and membrane integrity remain intact. Mechanistically, CD160 associates with the endocytic receptor LRP1 as demonstrated by proximity ligation assay, lipid-raft co-immunoprecipitation and super-resolution fluorescence microscopy. Both receptors appear in a common complex, and two independent computational methods converge on the first ligand-binding cluster of LRP1 as the interface. Silencing CD160 or LRP1 abolishes the anti-angiogenic response mediated by the antibody. Under a chloroquine clamp, engagement raises autophagic flux in a CD160- and LRP1-dependent manner, and lysosomal or LDL-receptor-family blockade removes the anti-sprouting effect. CD160 therefore acts as an inducible endothelial checkpoint that suppresses sprouting through autophagic flux. Thus, CD160 represents an inducible endothelial checkpoint that is activated in a pro-angiogenic environment, and targeting CD160 restrains pathological angiogensis.
ER -