Project Details
Projekt
Altersbedingte Veränderungen der Epithel- und T-Zell-Interaktion beeinträchtigen die Regenerationsfähigkeit der Lunge
Applicants
Dr. Maja Funk; Professorin Dr. Mareike Lehmann
Subject Area
Cell Biology
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 564756364
Direct cell-cell interactions are crucial for development, organ function, and tissue homeostasis but require tight regulation to prevent physiological dysfunction. A key example is immune-epithelial crosstalk in barrier organs like the lung, skin, and gastrointestinal tract, which ensures epithelial integrity and a coordinated immune response to environmental stimuli. Importantly, with age, epithelial and immune cell compartments undergo profound alterations that can impair tissue homeostasis, regenerative dysfunction, and lead to chronic diseases. As a critical barrier organ, the lung is particularly vulnerable to these aging-driven changes, resulting in a high prevalence of age-related diseases such as Chronic Obstructive Pulmonary Disease (COPD) and Idiopathic Pulmonary Fibrosis (IPF). While epithelial and immune cells are known to undergo age-related decline, the precise mechanisms by which their interactions contribute to tissue aging, especially on the level of epithelial cells, remain poorly understood. Based on our preliminary findings, we hypothesize that the reshaping of T cell compartments and functions during aging disrupts epithelial homeostasis and regeneration by promoting aging phenotypes in epithelial cells. In turn, aged epithelial cells alter their interaction properties with immune cells, further driving T cell dysfunction. This project aims to uncover the molecular mechanisms underlying these bidirectional interactions and the signaling hierarchies and explore therapeutic strategies to restore epithelial function in the aged lung. Thus, our project will have a significant impact by addressing a fundamental gap in understanding how epithelial-T cell interactions drive lung aging and age-related diseases. To this end, we will first create a comprehensive functional atlas of epithelial-T cell interactions across the lifespan, highlighting how aging reshapes cellular niches and alters immune-epithelial crosstalk. Next, we will focus on uncovering key molecular mechanisms using heterochronic organoid models to dissect signaling pathways driving epithelial dysfunction. We will provide critical insights into how aged T cells contribute to reduced epithelial regenerative capacity and impaired barrier function. Finally, we will perform mechanistic studies and target age-related impaired interactions and modify epithelial cells to reverse T cell-induced ageing phenotypes. This should provide the basis for the development of therapeutic strategies to restore epithelial function in the future.
DFG Programme
Priority Programmes
