Lenny Pommerolle, Guillaume Beltramo, Leo Biziorek, Marin Truchi, Alexandre Magno Maneschy Dias, Lucile Dondaine, Julie Tanguy, Nicolas Pernet, Victor Goncalves, Alexanne Bouchard, Marie Monterrat, Grégoire Savary, Nicolas Pottier, Kjetil Ask, Martin R J Kolb, Bernard Mari, Carmen Garrido, Bertrand Collin, Philippe Bonniaud, Olivier Burgy, Françoise Goirand, Pierre-Simon Bellaye
Thorax 2024 Jul 20Interstitial 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. 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. 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. These findings indicate that M2 macrophages may be relevant theranostic targets for personalised medicine for patients with PPF. © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Lenny Pommerolle, Guillaume Beltramo, Leo Biziorek, Marin Truchi, Alexandre Magno Maneschy Dias, Lucile Dondaine, Julie Tanguy, Nicolas Pernet, Victor Goncalves, Alexanne Bouchard, Marie Monterrat, Grégoire Savary, Nicolas Pottier, Kjetil Ask, Martin R J Kolb, Bernard Mari, Carmen Garrido, Bertrand Collin, Philippe Bonniaud, Olivier Burgy, Françoise Goirand, Pierre-Simon Bellaye. CD206+ macrophages are relevant non-invasive imaging biomarkers and therapeutic targets in experimental lung fibrosis. Thorax. 2024 Jul 20
PMID: 39033028
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