Immune Cells Shape Lung Development and Growth, Allow Developments for Treatment of Asthma, COPD

Research findings published in Science Immunology indicate that immune cells play an active and intimate role in directing the growth of lung tissue during development. The findings offer insights to better understand and treat respiratory conditions, such as chronic obstructive pulmonary disease and asthma.

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The study, which was the first of its kind according to the authors, shows a coordination between the immune and respiratory symptoms present in early development. Using multiple techniques such as single cell sequencing and experiments with lung cell cultures, the researchers determined whether or not the immune system influences how the lungs grow. Investigators looked at immune cells in early human lungs from 5 to 22 weeks of development in the study.

Immune cells, which make up a significant portion of the airways and mature lungs, have critical gas exchange and barrier functions to protect against infections of the respiratory tract; however, compared to structural or lining cell types, the specific roles of immune cells in the developing organ were previously unexplored.

“By adopting a focused strategy in mapping the immune system, we reveal a symbiotic relationship between immune cells and developing lungs. These detailed insights open the door to potential regenerative therapies in not only the lung, but in other vital human organs,” said co-first study author Jo Barnes, PhD, BSc, University College of London (UCL) Division of Medicine, London, United Kingdom, in a press release.

The study authors identified key regulators of lung development, such as the signaling molecules IL-1β and IL-13, which facilitate the coordination of lung stem cell differentiation into specialized mature cell types. Further, the authors detected an infiltration of innate cells—innate lymphoid cells, natural killer cells, myeloid cells, and progenitor cells—were followed by adaptive immune cells.

"We now know immune-epithelial crosstalk is a feature of early lung development,” said senior author Marko Nikolić, PhD, MB BChir, honorary consultant in respiratory medicine, UCL Division of Medicine, in the press release. “This vital baseline of healthy lung development will help us understand what happens when lung developmental processes get disrupted, for example in preterm births, which can lead to respiratory deficiencies.”

According to the authors, the findings significantly change the understanding experts have of the immune and epithelial interactions which are necessary for lung maturation. In addition, the investigators note that early immune disturbances can manifest as lung diseases in pediatric patients. The study findings have the potential to contribute to the development of new therapeutic approaches for regenerating lung tissue that was previously damaged, as well as the restoration of lung function.

“The active participation of immune cells expands the possibilities for understanding and addressing impaired lung formation. What is super exciting about this mechanism is that it may well apply in other organ systems too,” said senior study author Kerstin Meyer, BSc, PhD, Wellcome Sanger Institute, in the press release.

Reference

Wellcome Trust Sanger Institute. Immune cells shape lung before birth and provide new avenues for treating respiratory diseases. News release. December 15, 2023. Accessed January 2, 2024. https://www.eurekalert.org/news-releases/1011176