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CD206+ macrophages are relevant non-invasive imaging biomarkers and therapeutic targets in experimental lung fibrosis.
Pommerolle, Lenny; Beltramo, Guillaume; Biziorek, Leo; Truchi, Marin; Dias, Alexandre Magno Maneschy; Dondaine, Lucile; Tanguy, Julie; Pernet, Nicolas; Goncalves, Victor; Bouchard, Alexanne; Monterrat, Marie; Savary, Grégoire; Pottier, Nicolas; Ask, Kjetil; Kolb, Martin R J; Mari, Bernard; Garrido, Carmen; Collin, Bertrand; Bonniaud, Philippe; Burgy, Olivier; Goirand, Françoise; Bellaye, Pierre-Simon.
Afiliación
  • Pommerolle L; HSP-pathies Team, INSERM U1231 CTM Labex LIPSTIC and Label of Excellence from la Ligue National Contre le Cancer, Dijon, France.
  • Beltramo G; HSP-pathies Team, INSERM U1231 CTM Labex LIPSTIC and Label of Excellence from la Ligue National Contre le Cancer, Dijon, France.
  • Biziorek L; Pneumology and Respiratory Intensive Care, CHU Dijon, Dijon, France.
  • Truchi M; Reference Center for Rare Pulmonary Diseases, OrphaLung Network, RespiFil, CHU Dijon Bourgogne, Dijon, France, Valbonne, France.
  • Dias AMM; Faculty of Medicine and Pharmacy, University of Burgundy, Dijon, France, Dijon, France.
  • Dondaine L; HSP-pathies Team, INSERM U1231 CTM Labex LIPSTIC and Label of Excellence from la Ligue National Contre le Cancer, Dijon, France.
  • Tanguy J; Université Côte d'Azur, IPMC, UMR CNRS 7275 Inserm 1323, IHU RespiERA, Valbonne, France.
  • Pernet N; Team IMATHERA, Centre Georges François Leclerc, Dijon, France.
  • Goncalves V; HSP-pathies Team, INSERM U1231 CTM Labex LIPSTIC and Label of Excellence from la Ligue National Contre le Cancer, Dijon, France.
  • Bouchard A; Reference Center for Rare Pulmonary Diseases, OrphaLung Network, RespiFil, CHU Dijon Bourgogne, Dijon, France, Valbonne, France.
  • Monterrat M; HSP-pathies Team, INSERM U1231 CTM Labex LIPSTIC and Label of Excellence from la Ligue National Contre le Cancer, Dijon, France.
  • Savary G; Faculty of Medicine and Pharmacy, University of Burgundy, Dijon, France, Dijon, France.
  • Pottier N; Institut de Chimie Moléculaire de l'Université de Bourgogne, UMR 6302, CNRS, Université de Bourgogne, Dijon, France.
  • Ask K; Team IMATHERA, Centre Georges François Leclerc, Dijon, France.
  • Kolb MRJ; Team IMATHERA, Centre Georges François Leclerc, Dijon, France.
  • Mari B; FHU-OncoAge, CNRS, IPMC, Université Côte d'Azur, Valbonne, France.
  • Garrido C; FHU-OncoAge, CNRS, IPMC, Université Côte d'Azur, Valbonne, France.
  • Collin B; Department of Medicine, Pathology, and Molecular Medicine, McMaster University, Dijon, Ontario, Canada.
  • Bonniaud P; Department of Medicine, Pathology, and Molecular Medicine, McMaster University, Dijon, Ontario, Canada.
  • Burgy O; Université Côte d'Azur, IPMC, UMR CNRS 7275 Inserm 1323, IHU RespiERA, Valbonne, France.
  • Goirand F; HSP-pathies Team, INSERM U1231 CTM Labex LIPSTIC and Label of Excellence from la Ligue National Contre le Cancer, Dijon, France.
  • Bellaye PS; Reference Center for Rare Pulmonary Diseases, OrphaLung Network, RespiFil, CHU Dijon Bourgogne, Dijon, France, Valbonne, France.
Thorax ; 2024 Jul 20.
Article en 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.
Palabras clave

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: Thorax Año: 2024 Tipo del documento: Article País de afiliación: Francia

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: Thorax Año: 2024 Tipo del documento: Article País de afiliación: Francia