Research sheds new insights into development of lung macrophages in humans

The lungs are exposed to microorganisms like viruses and bacteria from the moment of the first breath. People are protected from most diseases at a young age, thanks to immune cells in the lungs called macrophages.

Research sheds new insights into development of lung macrophages in humans
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Scientists from Karolinska Institutet reveal how lung macrophages evolve. The new insights can assist in preventing organ damage and are significant for the continuous development of important lung disease therapies. The study was published in the Journal of Experimental Medicine.

The development of lung macrophages occurs in humans right from birth when inhaled air inflates the lungs for the first time. Despite the significance of lung macrophages in the immune system, it was not known earlier about how they develop in humans as in vivo studies in humans are not easy to conduct.

Researchers from Karolinska Institutet have now been able to directly investigate the growth of human macrophages in a living lung using a model. The researchers revealed that lung macrophages can develop in two ways.

In the first type of development, lung macrophages originate from precursor cells that are already present in the fetus’ liver.”

Tim Willinger, Associate Professor, Department of Medicine, Huddinge, Karolinska Institutet

Tim Willinger who led the study added, “After we are born, these precursor cells move from the liver to the lungs via the bloodstream. In the lungs, they are then exposed to various growth factors, which helps them to develop into ’mature’ lung macrophages.

The second type of development occurs later in life. At that point they develop from adult precursor cells, so-called monocytes, which are found in the blood.”

Tim Willinger, Associate Professor, Department of Medicine, Huddinge, Karolinska Institutet

Similar gene expression but different functions

The researchers also looked at whether the origin of lung macrophages has an impact on their function. They found that lung macrophages of all origins had identical gene expressions but performed diverse functions.

We discovered that fetal precursor cells divide faster than the adult precursor cells. The fetal precursor cells therefore populate the lungs faster, which is important early on in life to quickly remove microorganisms and other inhaled particles.”

Elza Evren, Study First Author and Doctoral Student, Karolinska Institutet

Elza Evren is a student at Tim Willinger’s research group.

Interferon, a protein that protects against viral infections, was discovered to robustly stimulate lung macrophages taken from adult precursor cells. As a result, it’s extremely likely that this kind of lung macrophage plays a crucial role in the immune system’s virus-fighting efforts.

These lung macrophages are similarly comparable to pro-inflammatory macrophages, which may become overactive and lead to significant lung damage in disorders like COVID-19, according to the researchers.

Limit lung damage and promote new treatments

The current studies lead to a better knowledge of lung macrophage origins and functions. The scientists found a human fetal progenitor cell that may be used to regenerate tissue-protective macrophages, reduce organ damage, and boost tissue regeneration in an infected lung. These results might help scientists design novel therapies for a variety of lung infections.

Journal reference:

Evren, E., et al. (2022) CD116+ fetal precursors migrate to the perinatal lung and give rise to human alveolar macrophages. Journal of Experimental Medicine.


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