Integrated multi-omics profiling landscape of organising pneumonia

Area of Science:

• Pulmonary Medicine
• Cell Biology
• Metabolomics

Background:

• Organising pneumonia (OP) is a lethal interstitial lung disease.
• Lipid metabolism reprogramming is a hallmark of various diseases.
• The role of ceramides in OP pathogenesis was previously unclear.

Purpose of the Study:

• Investigate the role of lipid metabolism reprogramming in OP.
• Focus on the involvement of inflammation and fibrosis in OP.
• Elucidate the specific mechanisms of lipid metabolism in OP.

Main Methods:

• Utilized comprehensive multi-omics profiling (scRNA-seq, spatial transcriptomics, proteomics, metabolomics).
• Employed an OP mouse model and analyzed macrophage-specific molecular mechanisms.
• Investigated the impact of CD36 deficiency in alveolar macrophages.

Main Results:

• Significant association found between OP and lipid metabolism reprogramming, with altered expression of genes like CD36, SCD1, and CES1 in macrophages.
• CD36 deficiency in macrophages increased ceramide levels, leading to mitochondrial dysfunction and reduced macrophage numbers via ferroptosis.
• Macrophage-derived DPP7 and FABP4 influenced epithelial cell fibrosis.

Conclusions:

• CD36 inhibits the ferroptosis pathway (SLC3A2/GPX4) in OP alveolar macrophages by regulating lipid metabolism.
• CD36 exhibits anti-ferroptosis and anti-fibrosis effects in OP, partly mediated by ceramides.
• Findings contribute to understanding OP mechanisms and suggest CD36 as a potential therapeutic target.