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

Research Division of Infection Biology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.Research Division of Infection Biology, Department of Medicine I, Medical University of Vienna, Vienna, Austria. · pubmed

Paper

Abstract

Pulmonary fibrosis is an incurable disease that manifests with advanced age. Yet, how hematopoietic aging influences immune responses and fibrosis progression remains unclear. Using heterochronic bone marrow transplant mouse models, we found that an aged bone marrow exacerbates lung fibrosis irrespective of lung tissue age. Upon lung injury, there was an increased accumulation of monocyte-derived alveolar macrophages (Mo-AMs) driven by cell-intrinsic hematopoietic aging. These Mo-AMs exhibited an enhanced profibrotic profile and stalled maturation into a homeostatic, tissue-resident phenotype. This delay was shaped by cell-extrinsic environmental signals such as reduced pulmonary interleukin-10 (IL-10), perpetuating a profibrotic macrophage state. We identified regulatory T cells (T

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Research summary

The paper claims that aged bone marrow exacerbates lung fibrosis by promoting the persistence of profibrotic macrophages. This research is relevant as it explores the mechanisms by which hematopoietic aging influences immune responses and contributes to age-related diseases, potentially addressing underlying causes of aging-related pathologies.

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