New study reveals how the lung's immune cells develop after birth

Date:
January 12, 2022
Source:
Karolinska Institutet
Summary:
From our first breath, our lungs are exposed to microorganisms,
such as bacteria and viruses. Thanks to immune cells in the lungs,
so-called macrophages, we are protected from most infections at
an early age.

Researchers now show how lung macrophages develop; new findings
that can help to reduce organ damage and that are significant for
the continued development of important lung disease treatments.



FULL STORY ==========================================================================
From our first breath, our lungs are exposed to microorganisms, such
as bacteria and viruses. Thanks to immune cells in the lungs, so-called macrophages, we are protected from most infections at an early age. In a
new study published in the Journal of Experimental Medicine, researchers
from Karolinska Institutet show how lung macrophages develop; new findings
that can help to reduce organ damage and that are significant for the
continued development of important lung disease treatments.


==========================================================================
Lung macrophages begin to develop in humans from birth when the lungs
are first inflated with inhaled air. Despite the importance of lung
macrophages in the immune system, it has not been previously known how
they develop in humans, since in-vivo studies in humans are difficult
to conduct.

However, with the help of a model, researchers at Karolinska Institutet
have now been able to directly study the development of human macrophages
in a living lung. In the study, it was discovered that lung macrophages
develop in two different ways.

"In the first type of development, lung macrophages originate from
precursor cells that are already present in the fetus' liver," says Tim Willinger, associate professor at the Department of Medicine, Huddinge, Karolinska Institutet, who has led the study. "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." Similar gene expression
but different functions The researchers also investigated whether the
origin of the lung macrophages affects their function. Here they could
see that the lung macrophages, regardless of their origin, had a similar
gene expression but with different functions.

"We discovered that fetal precursor cells divide faster than the adult precursor cells," says the study's first author Elza Evren, doctoral
student in Tim Willinger's research group. "The fetal precursor cells
therefore populate the lungs faster, which is important early on in
life to quickly remove microorganisms and other inhaled particles."
The lung macrophages derived from adult precursor cells were instead
found to be strongly activated by interferon, a protein that has the
task to defend against viral infections. It is therefore very likely
that this particular type of lung macrophage has an important function
within the immune system to help fight viruses.

The researchers were also able to see that these lung macrophages are
similar to pro-inflammatory macrophages, which can become overactivated
and contribute to serious lung damage in diseases such as COVID-19.

Limit lung damage and promote new treatments The new findings
contribute to a better understanding of the origin and function of
lung macrophages. The human fetal progenitor cell that the researchers
have identified is a potential cell that can be targeted to regenerate tissue-protective macrophages, limit organ damage and promote tissue
repair in an injured lung. These findings can also support the development
of new treatments for a number of lung diseases.

The study was supported by grants from Swedish Research Council,
SciLifeLab, Knut and Alice Wallenberg Foundation, Karolinska Institutet,
Centre for Innovative Medicine (CIMED), Region Stockholm, the Swedish Heart-Lung Foundation, Petrus och Augusta Hedlunds Stiftelse and the Royal Swedish Academy of Sciences. One of the authors from Yale University
has reported conflicts of interest, which are described in detail in
the scientific paper.

========================================================================== Story Source: Materials provided by Karolinska_Institutet. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Elza Evren, Emma Ringqvist, Jean-Marc Doisne, Anna Thaller, Natalie
Sleiers, Richard A. Flavell, James P. Di Santo, Tim Willinger. CD116
fetal precursors migrate to the perinatal lung and give rise to
human alveolar macrophages. Journal of Experimental Medicine,
2022; 219 (2) DOI: 10.1084/jem.20210987 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/01/220112105620.htm
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