CD206+ macrophages are relevant non-invasive imaging biomarkers and therapeutic targets in experimental lung fibrosis.
Thorax
; 2024 Jul 20.
Article
in En
| MEDLINE
| ID: mdl-39033028
ABSTRACT
BACKGROUND:
Interstitial lung diseases (ILDs) include a large number of diseases associated with progressive pulmonary fibrosis (PPF), including idiopathic pulmonary fibrosis (IPF). Despite the rarity of each of the fibrotic ILDs individually, they cumulatively affect a considerable number of patients. PPF is characterised by an excessive collagen deposition leading to functional decline.OBJECTIVES:
Therapeutic options are limited to nintedanib and pirfenidone which are only able to reduce fibrosis progression. CD206-expressing M2 macrophages are involved in fibrosis progression, and whether they may be relevant therapeutic targets or biomarkers remains an open question.RESULTS:
In our study, CD206+ lung macrophages were monitored in bleomycin-induced lung fibrosis in mice by combining flow cytometry, scRNAseq and in vivo molecular imaging using a single photon emission computed tomography (SPECT) radiopharmaceutical, 99mTc-tilmanocept. The antifibrotic effect of the inhibition of M2 macrophage polarisation with a JAK inhibitor, tofacitinib, was assessed in vivo. We demonstrate that CD206-targeted in vivo SPECT imaging with 99mTc-tilmanocept was able to accurately detect and quantify the increase in CD206+ macrophages from early to advanced stages of experimental fibrosis and ex vivo in lung biopsies from patients with IPF. CD206-targeted imaging also specifically detected a decrease in CD206+ lung macrophages on nintedanib and tofacitinib treatment. Importantly, early in vivo imaging of CD206+ macrophages allowed the prediction of experimental lung fibrosis progression as well as nintedanib and tofacitinib efficacy.CONCLUSIONS:
These findings indicate that M2 macrophages may be relevant theranostic targets for personalised medicine for patients with PPF.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Thorax
Year:
2024
Document type:
Article
Affiliation country:
Francia