Human lung fibroblasts may modulate dendritic cell phenotype and function: results from a pilot in vitro study

International audienceAbstractIn human lung fibrotic lesions, fibroblasts were shown to be closely associated with immature dendritic cell (DC) accumulation. The aim of the present pilot study was to characterize the role of pulmonary fibroblasts on DC phenotype and function, using co-culture of lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) and from control patients, with a DC cell line MUTZ-3. We observed that co-culture of lung control and IPF fibroblasts with DCs reduced the expression of specific DC markers and down-regulated their T-cell stimulatory activity. This suggests that pulmonary fibroblasts might sustain chronic inflammation in the fibrotic lung by maintaining in situ a pool of immature DCs

Fibroblasts: the missing link between fibrotic lung diseases of different etiologies?

CommentaryInternational audienc

Rôle de la voie de signalisation FGF10/FGFR2b lors de l'ontogenèse du poumon et de la glande mammaire

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

New targets in idiopathic pulmonary fibrosis: from inflammation and immunity to remodeling and repair

Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic respiratory disease whose incidence and prevalence are increasing. Recent evidence has led to a change of paradigm regarding understanding of the underlying pathophysiology. In parallel, we have witnessed the development and rise of the first anti-fibrotic drugs, namely pirfenidone and nintedanib. However, with clinical results being below expectations there is a clear need for new medications in this field. Areas covered: After covering new mechanisms involved in IPF pathogenesis, the present review discusses current clinical trials and deciphers potential new targets in light of in vitro and in vivo experimental studies. Expert Opinion: All in all, we believe that future development will require (1) a significant improvement in experimental models, (2) a proper selection and characterization of patients, allowing us to foresee which will respond to a given treatment and (3) an evaluation of combined therapies, targeting different pathways

Late Breaking Abstract-PRRX1 inhibition decreases fibrosis in the bleomycin-induced lung fibrosis model in mice

International audienc

Chaotic activation of developmental signalling pathways drives idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is characterised by an important remodelling of lung parenchyma. Current evidence indicates that the disease is triggered by alveolar epithelium activation following chronic lung injury, resulting in alveolar epithelial type 2 cell hyperplasia and bronchiolisation of alveoli. Signals are then delivered to fibroblasts that undergo differentiation into myofibroblasts. These changes in lung architecture require the activation of developmental pathways that are important regulators of cell transformation, growth and migration. Among others, aberrant expression of profibrotic Wnt-β-catenin, transforming growth factor-β and Sonic hedgehog pathways in IPF fibroblasts has been assessed. In the present review, we will discuss the transcriptional integration of these different pathways during IPF as compared with lung early ontogeny. We will challenge the hypothesis that aberrant transcriptional integration of these pathways might be under the control of a chaotic dynamic, meaning that a small change in baseline conditions could be sufficient to trigger fibrosis rather than repair in a chronically injured lung. Finally, we will discuss some potential opportunities for treatment, either by suppressing deleterious mechanisms or by enhancing the expression of pathways involved in lung repair. Whether developmental mechanisms are involved in repair processes induced by stem cell therapy will also be discussed