Actualités
Séminaires

Ana Pardo-Saganta, PhD

Professor Lung Inflammation and Repair

Institute for Lung Health - Justus Liebig University

German Center for Lung Research, GIESSEN (Germany)

"Coordinated healing: heterotypic cellular interactions in lung injury and repair"

host : A. MARAVER (IRCM)

Chronic lung disease such as IPF or COPD develops over extended periods of time and are
characterized by failure in mechanisms of repair (1,2). Both pathologies are considered age-related
diseases exhibiting most of the hallmarks of aging including stem cell exhaustion and altered
intercellular communication (3). In the last years, novel epithelial progenitor cells have been identified
and demonstrated to contribute to lung repair. In fact, distinct subpopulations of alveolar type (AT) 2
cells have been shown to have higher regenerative capacity (4-8). Recent findings shed light to the
mechanisms of regeneration of the alveolar epithelium (8-11); however, a better understanding of the
coordinated processes of tissue repair from different stem cell pools after injury is crucial to restore
the delicate lung architecture. Our research focuses on the study of the interplay between these
epithelial progenitor populations and neighboring cell types of their microenvironment in the
development of lung disease.
It is now generally accepted that epithelial cell loss or dysfunction drives the development of lung
fibrosis (12-15). We have identified an additional function for AT2 cells that in addition to serve as
adult stem cells of the alveolar epithelium can play a profibrotic role directly activating adjacent
fibroblast. This communication is mediated by the Notch pathway and their blockade seems to
attenuate the fibrotic phenotype, revealing a potential therapy for IPF, a fatal disease with no cure, a
median survival of 3-5 years post-diagnosis and whose incidence in increasing in the last years (1).
Thus, our findings support the notion that the pathophysiology of pulmonary fibrosis relies in part, on
the Notch-regulated interaction between aberrant cellular populations of the fibrotic lung and that
unravelling this complex microenvironment is critical to find efficient treatments for IPF.
References
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