Using a fibrosis model in young vs aged mice, Farhat and Knapp show that an aged bone marrow autonomously produced more profibrotic Mo-AMs, had a reduced availability of Tregs-derived IL-10 causing exacerbated lung fibrosis. [4/n]

www.science.org/doi/10.1126/...

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10/ Our study highlights the impact of an aging bone marrow on the lung and defines a Treg–IL-10–macrophage axis that becomes dysfunctional with age. It offers a potential immune axis to reduce fibrotic severity and reframes how we understand age-related tissue dysfunction.

9/ Conversely, transplanting young bone marrow into aged mice reduced disease severity and profibrotic macrophage numbers - showing that the age of the bone marrow shaped fibrotic outcome.

8/ Blocking IL-10 or depleting Tregs in young mice reproduced the aged bone marrow phenotype. Mo-AMs failed to mature and fibrosis worsened.

7/ This failure was linked to reduced IL-10 in the lung, a key anti-inflammatory cytokine.
The reason: fewer IL-10–producing regulatory T cells (Tregs) in the lungs of mice with aged bone marrow.

6/ We found that not only were Mo-AM numbers higher, but these aged Mo-AMs failed to transition into a tissue-resident, homeostatic state. They remained persistently inflammatory and profibrotic over time.

5/ Aged bone marrow caused increased recruitment of monocytes and accumulation of monocyte-derived alveolar macrophages (Mo-AMs)—key immune players in fibrosis.

4/ Transplanting aged bone marrow cells into young mice led to more severe lung fibrosis after injury—despite the lung tissue being young.
This points to the aging immune system as a key driver of fibrotic progression.

3/ We asked: Can hematopoietic aging drive lung fibrosis? To test this, we used a bone marrow transplant model to decouple immune and lung tissue aging.

2/ Lung fibrosis is a devastating, end-stage disease with limited treatment options. Aging is the strongest risk factor, but how immune aging contributes remains poorly understood