Molecular and cellular characterization of CD274Pos injury-activated alveolar epithelial progenitor cells in human lungs

• Applicant: Negah Ahmadvand, Ph.D.
• Subject Area: Cell Biology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 515100370

Alveolar epithelial type 2 (AT2) cells are considered distal lung stem cells as they can self-renew and differentiate into alveolar epithelial type 1 (AT1) cells which form the primary gas exchange surface of the alveolus. AT2 cell dysfunction plays a detrimental role in epithelium repair in lung diseases, e.g., Idiopathic Pulmonary Fibrosis (IPF), which is a progressive and degenerative lung disease with high mortality. Therefore, understanding the molecular mechanisms of AT2 progenitor cell behavior to restore their regenerative capabilities in IPF lungs is critical to finding therapeutic approaches. This project aims to study the endogenous regenerative capacity mediated by a newly identified subpopulation of AT2, i.e., injury-activated alveolar progenitors (IAAPs), which are enriched in CD274 (PD-L1) gene expression. To do so, the potential of IAAPs to restore the alveolar epithelium barrier of the diseased lung will be investigated in an in-vivo injury model. Collectively, three main objectives will be followed: 1- Understanding molecular mechanism regulating activation, proliferation, and differentiation of IAAPs CD274Pos into AT2 or AT1 cells 2- Investigation of the potential regenerative capacity of IAAPs CD274Pos to replace impaired alveolar epithelium in a fibrosis mouse model with transplantation of healthy human IAAPs progenitor cells into an injured lung 3- Identification of putative IAAPs-immune cells interaction and thereby the role of reciprocal epithelium-immune system interaction in lung repair Finally, the proposed research objectives shed light on the efficient regeneration of AT2 and AT1 cells, which can be potentially used for treating life-threatening lung diseases.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Purushothama Rao Tata, Ph.D.