Lung fibrosis is a devastating disease with lung transplant as the only effective treatment currently. Aging is the strongest risk factor, but this was so far thought to be driven by aging lung tissue. Now, research led by Prof. Sylvia Knapp and Dr. Riem Gawish at the Medical University Vienna, supported by the SFB, with first author Asma Farhat, has found that it is the aging hematopoietic system—specifically immune cells infiltrating the lungs—that drives fibrosis after lung injury.
In a study published in Science Immunology, Asma Farhat and team found that transplanting aged bone marrow into young mice triggered accumulation of persistent, profibrotic macrophages—even with young lung tissue. Asma Farhat et al. identified interleukin-10 (IL-10) produced by regulatory T cells (Tregs) as essential for suppressing the inflammatory and fibrosis-promoting properties of these macrophages, but found that with age, this protective mechanism becomes compromised, resulting in chronic inflammation and fibrosis. Giving young bone marrow to aged mice reduced macrophage accumulation and fibrosis, highlighting immune aging as the key driver and a potential therapeutic target for reducing disease burden.
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 Starkl, Nicole Boucheron, Jörg Menche, Joris van der Veeken, Wilfried Ellmeier, Anna-Dorothea Gorki, Clarissa Campbell, Riem Gawish, Sylvia Knapp.
science.org/doi/10.1126/sciimmunol.adk5041
