(Vienna, 31 March 2025) Pulmonary fibrosis is a severe, chronic disease that predominantly affects people at an advanced age. Since there are currently no specific treatments, lung transplantation often remains the only option to prolong the patient's life. A research team from MedUni Vienna has now discovered that an ageing immune system plays a significant role in the development and progression of the disease. The study lays the foundation for the development of new immunomodulation-based therapies and has been published in the leading journal "Science Immunology".
As part of the research work, the team led by Sylvia Knapp and Riem Gawish (MedUni Vienna's Department of Medicine I) was able to demonstrate for the first time the importance of the age of certain immune cells in the development of idiopathic pulmonary fibrosis (IPF). IPF is a severe, chronic disease in which there is an excessive deposition of connective tissue. This leads to an increasing hardening of the lung tissue, restricted breathing and ultimately death. Since there are currently no specific therapies, lung transplantation often remains the only treatment option. The disease mainly occurs in old age, which has so far been attributed to age-related changes in lung structural cells.
Targeted rejuvenation of the immune system
As the researchers' current investigations have shown, contrary to previous opinion, it is not primarily the lung structural cells themselves that are responsible for the increasing risk of IPF over the years, but the ageing immune system. Using a mouse model, it was possible to show that the transplantation of old immune cells worsens fibrosis in young animals, while targeted rejuvenation of the immune system prevents the disease in older conspecifics. This is because, in old age, certain immune cells (profibrotic macrophages) increasingly migrate into the lungs, where they promote the formation of pathological connective tissue. At the same time, there is a lack of the necessary activation of anti-inflammatory counterparts, the regulatory T cells. As they age, they produce less of the anti-inflammatory factor interleukin-10, which contributes to the further progression of the disease. "The interleukin-10 produced by T cells is important for suppressing the profibrotic effects of macrophages, and it is precisely this important mechanism that appears to no longer function in old age," says the first author Asma Farhat.
These findings have laid the foundation for an innovative therapeutic approach based on the modulation of immune cells that could offer an alternative to lung transplantation. Further studies are needed to verify the results and to pursue the chosen path.
Publication: Science Immunology
An aging bone marrow exacerbates lung fibrosis by fueling profibrotic macrophage persistence.
Asma Farhat, Mariem Radhouani, Florian Deckert, Sophie Zahalka, Lisabeth Pimenov, Alina Fokina, Anna Hakobyan, Felicitas Oberndorfer, Jessica Brösamlen, Anastasiya Hladik, Karin Lakovits, Fanzhe Meng, Federica Quattrone, Louis Boon, Cornelia Vesely, Philipp Starkl1, Nicole Boucheron, Jörg Menche, Joris van der Veeken, Wilfried Ellmeier, Anna-Dorothea Gorki, Clarissa Campbell, Riem Gawish, Sylvia Knapp.
https://www.science.org/doi/10.1126/sciimmunol.adk5041