The human lung is the largest surface that is in continuous contact with the inhaled air, containing numerous innocuous environmental antigens, including allergens as pollen or house dust mite (HDM) particles. The immune system should normally not react to these harmless substances. On the other hand, the lung can be the entrance site for pathogens including viruses, bacteria and fungi, and to these, a vigorous immune response should be initiated. Recent studies suggest critical immunogenic and immunoregulatory functions of airway epithelium.

In response to inhaled antigens, Airway Epithelial Cells release a variety of chemokines (like CCL2 and CCL20), cytokines like GM-CSF, Il-1 family members and a triad including IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) and growth factors like VEGFs. While these molecules are produced by airway epithelial cells, these factors affect the functions and integrity of airway epithelium itself either directly or indirectly through activation of airway immune cells (like dendritic cells) but also through remodeling of lymphatic vasculature. Lymphatic vessels (LVs) exist in most vascularized organs where they contribute to fluid homeostasis by absorbing tissue fluid and draining it into the venous circulation. Edema, a cardinal sign of inflammation and clinically significant feature of inflammatory disease, results when the amount of leakage from inflamed blood vessels exceeds the capacity of lymphatic vessels for drainage. In addition to fluid homeostasis, LVs are also important for immune surveillance as they allow for the directed emigration of inflammatory cells, DCs and lymphocytes to the draining lymph nodes. Furthermore, LVs in lymph nodes (LNs) and peripheral tissues are highly plastic; hence, LVs undergo proliferation or remodeling during various pathological conditions such as inflammation, and might strongly impact the ongoing inflammatory immune response in the lung.  These processes provide signal input to the central lymphoid organs and thus perpetuate inflammation, conversely to their role in edema draining which might be broadly anti-inflammatory. Despite its diametrical impact on the pathogenesis of lung chronic diseases relatively little is known about lung lymphangiogenesis.

In this project, using several approaches (in vivo: animal models; in vitro: cell culture) like fluorescent microscopy, cytometry or RNA sequencing, we aim to decipher the time course, extent, the molecular mechanisms and the functional consequences of inflammation triggered lung remodelling by addressing the following questions:

1. Origin and behavior of lung cells in airway diseases?
2. What are the cellular and molecular signals driving remodelling?
3. Which immune cell type(s) contributes to remodelling?
4. What are the functional consequences of remodelling?

So, a better understanding of lung remodeling (epithelium and lymphatic vasculature) in lung disease is paramount to find new therapeutic avenues.