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Noninvasive assessment of the lung inflammation-fibrosis axis by targeted imaging of CMKLR1.

Authors :
Mannes PZ
Adams TS
Farsijani S
Barnes CE
Latoche JD
Day KE
Nedrow JR
Ahangari F
Kaminski N
Lee JS
Tavakoli S
Source :
Science advances [Sci Adv] 2024 Jun 21; Vol. 10 (25), pp. eadm9817. Date of Electronic Publication: 2024 Jun 19.
Publication Year :
2024

Abstract

Precision management of fibrotic lung diseases is challenging due to their diverse clinical trajectories and lack of reliable biomarkers for risk stratification and therapeutic monitoring. Here, we validated the accuracy of CMKLR1 as an imaging biomarker of the lung inflammation-fibrosis axis. By analyzing single-cell RNA sequencing datasets, we demonstrated CMKLR1 expression as a transient signature of monocyte-derived macrophages (MDMφ) enriched in patients with idiopathic pulmonary fibrosis (IPF). Consistently, we identified MDMφ as the major driver of the uptake of CMKLR1-targeting peptides in a murine model of bleomycin-induced lung fibrosis. Furthermore, CMKLR1-targeted positron emission tomography in the murine model enabled quantification and spatial mapping of inflamed lung regions infiltrated by CMKLR1-expressing macrophages and emerged as a robust predictor of subsequent lung fibrosis. Last, high CMKLR1 expression by bronchoalveolar lavage cells identified an inflammatory endotype of IPF with poor survival. Our investigation supports the potential of CMKLR1 as an imaging biomarker for endotyping and risk stratification of fibrotic lung diseases.

Details

Language :
English
ISSN :
2375-2548
Volume :
10
Issue :
25
Database :
MEDLINE
Journal :
Science advances
Publication Type :
Academic Journal
Accession number :
38896611
Full Text :
https://doi.org/10.1126/sciadv.adm9817