CD47 Blockade Reprograms the Monocyte-Macrophage Axis to Promote Inflammation Resolution in Atherosclerosis.

Area of Science:

• Immunology
• Cardiovascular Disease
• Cell Biology

Background:

• Atherosclerosis is a major cause of cardiovascular death, driven by chronic inflammation and impaired efferocytosis (clearance of dead cells).
• The CD47-SIRPα axis acts as a "don't-eat-me" signal, hindering efferocytosis and promoting disease progression.
• Understanding how interventions targeting this pathway remodel established lesions is crucial.

Purpose of the Study:

• To investigate the impact of CD47 blockade on the immune cell landscape within established atherosclerotic lesions.
• To elucidate the mechanisms by which anti-CD47 therapy reshapes myeloid cell populations and restores efferocytic function.

Main Methods:

• Single-cell transcriptomics and monocyte fate mapping in murine atherosclerosis models.
• Functional analyses to assess efferocytosis and macrophage proliferation.
• Cross-species integration with human coronary artery single-cell data.

Main Results:

• CD47 blockade selectively reduced inflammatory Ly6C ^hi monocyte recruitment and local macrophage proliferation.
• Therapy enriched pro-efferocytic macrophage subsets, restoring in situ apoptotic cell clearance.
• A conserved TREM2 ^hi macrophage population with efferocytic machinery was identified across species.

Conclusions:

• CD47 blockade fundamentally reprograms the myeloid landscape in established atherosclerotic lesions.
• The therapy promotes a dual mechanism: suppressing inflammatory influx and enhancing efferocytic capacity.
• This approach offers a promising strategy for resolving vascular inflammation in atherosclerosis.