Leader(s)

• 

  Crestani Bruno

  • 01 40 25 86 86
  • bruno.crestani@inserm.fr
• 

  Mailleux Arnaud

  • 0157277584
  • arnaud.mailleux@inserm.fr

Presentation

Our project aims to elucidate the mechanisms involved in the development of pulmonary fibrosis (PF) and identify new therapeutic targets. We primarily focus on idiopathic pulmonary fibrosis (IPF), a rare chronic fibrosing lung disease of unknown cause, while using PF associated with rheumatoid arthritis (RA) and systemic sclerosis (SSc) as models of autoimmune PF. Over the past decade, our team has focused on reactivation of developmental pathways, regulation of the abnormal fibroblast phenotype, and the genetics of pulmonary fibrosis. We are now expanding our efforts in two new directions: (1) identifying the immune and inflammatory components of PF and (2) understanding lung cancer development in the context of PF.

Our team comprises a diverse group of scientists (developmental and cellular biology, immunology) and clinician-researchers (adult pulmonologists, geneticists, immunologists, and pathologists). Our research spans the pathophysiology of fibrosing diseases, tumor development, inflammation, and lung immunology:

1. Differentiation and aberrant phenotypes of mesenchymal cells in PF
   (Leads: A. Mailleux, B. Crestani)

   • Identification of fibroblast subpopulations expressing the transcription factor PRRX1 associated with PF through lineage tracing in mice.
   • Characterization of PRRX1 isoforms in pulmonary fibrosis related to SSc.
   • Investigation of the potential involvement of pulmonary adipose tissue in IPF.

2. New immune mechanisms in PF
   (Leads: G. Helou, H. Flament)

   • Exploration of the role of immune checkpoints in regulating IPF.
   • Study of mucosa-associated invariant T (MAIT) cells in IPF and their interaction with the pulmonary microbiota.

3. Lung cancer and IPF
   (Leads: N. Poté, A. Cazes, A. Mailleux)

   • Identification of genes and signaling pathways associated with carcinogenesis in patients with IPF.
   • Role of the fibrotic environment in tumor growth in a preclinical murine model.

4. Genetics of pulmonary fibrosis
   (Leads: R. Borie, P. Dieudé, C. Kannengiesser)

   • Characterization of the genotype/phenotype correlation in carriers of mutations in telomerase-related genes (TRG) and their asymptomatic relatives.
   • Identification of somatic compensations to improve detection of TRG patients and understand the clinical impact.
   • Explanation of the pathophysiological basis of PF linked to PARN deficiency, a common TRG mutation.
   • Deciphering the genetics of interstitial lung diseases associated with RA.

These projects involve various methodologies, including transcriptomics, flow cytometry, mass spectrometry imaging, and preclinical murine models of pulmonary fibrosis (lineage tracing, organoids, and ex vivo organotypic culture of lung slices). Our team has the expertise and facilities necessary to perform these techniques directly or through established collaborations.