Mailleux / Crestani

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

Our team brings together a wide range of scientists (developmental and cell biology, immunology) and clinician-researchers (pulmonologists, geneticists, immunologists and pathologists). Our research focuses on the pathophysiology of fibrosing diseases, tumor development, inflammation, and pulmonary immunology:

1. Differentiation and aberrant phenotypes of mesenchymal cells in pulmonary fibrosis (Principal Investigators: A. Mailleux, B. Crestani)

• Identification of different fibroblast subpopulations expressing the PRRX1 transcription factor associated with pulmonary fibrosis by cell line in mice.
• Characterization of PRRX1 isoforms in pulmonary fibrosis associated with systemic sclerosis.
• Study of the potential involvement of pulmonary fibrosis Adipose tissue in idiopathic pulmonary fibrosis.

2. New immune mechanisms in pulmonary fibrosis (Lead researchers: G. Helou, H. Flament)

• Exploring the role of immune checkpoints in the regulation of idiopathic pulmonary fibrosis
• Study of mucosa-associated invariant T cells (MAIT) in idiopathic pulmonary fibrosis and their interaction with the pulmonary microbiota.

3. Lung Cancer and Idiopathic Pulmonary Fibrosis (Principal Investigators: N. Poté, A. Cazes, A. Mailleux)

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

4. Genetics of Pulmonary Fibrosis (Principal Investigators: R. Borie, P. Dieudé, C. Kannengiesser)

• Characterization of the genotype/phenotype correlation in telomerase-related gene (TRG) mutation carriers and their asymptomatic relatives.
• Identification of somatic compensations to improve screening for patients with TRG and understand the clinical impact.
• Explanation of the pathophysiological basis of pulmonary fibrosis (PF) linked to PARN deficiency, a common mutation in the TRG gene.
• These projects employ a variety of methodologies, including transcriptomic approaches, flow cytometry, mass spectrometry imaging, and preclinical murine models of pulmonary fibrosis (cell line, organoids, and ex vivo organotypic culture of lung slices). Our team has all the necessary expertise and facilities to implement these techniques, either directly or through established collaborations.