The researchers found that the immune cells they play an active and intimate role in directing the growth of human lung tissue during development, revolutionizing our understanding of early lung development and the role of immune cells outside of immunity.
The results of the study were published in Science Immunology.
Immune cells: here's what science says
The research offers new insights into understanding and treating respiratory conditions, such as chronic obstructive pulmonary disease (COPD). Respiratory diseases account for nearly 20% of all deaths of children under five worldwide.
The work reveals a surprising coordination between the immune and respiratory systems, much earlier in development than previously thought. This finding raises questions about the potential role of immune cells in other developing organs throughout the body.
Researchers at the Wellcome Sanger Institute, University College London (UCL) and their collaborators at EMBL's European Bioinformatics Institute have used advanced single-cell technologies to map the development of early human lung immune cells over time.
This study created a first-of-its-kind immune cell atlas of the developing lung. It is part of the international Human Cell Atlas initiative, which is mapping every cell type in the human body, to transform our understanding of health, infection and disease.
Immune cells make up a substantial portion of the mature airways and lungs, which have critical gas exchange and barrier functions, providing protection against respiratory tract infections. However, the roles of immune cells in the developing organ have remained unexplored with respect to structural or lining cell types. Recent findings confirm the presence of immune cells in human lungs after just five weeks of development.
To explore whether the immune system might influence how the lungs grow, the team studied immune cells in early human lungs from 5 to 22 weeks of development. They used various techniques, including single-cell sequencing and experiments with lung cell cultures, to see whether immune cells could influence the development of lung cells.
They identified key regulators of lung development, including the signaling molecules IL-1β and IL-13 that facilitate the coordination of lung stem cells that differentiate into specialized mature cell types.
The researchers detected an infiltration of innate immune cells, followed by adaptive immune cells. Innate cells included innate lymphoid cells (ILCs), natural killer (NK) cells, myeloid cells, and progenitor cells. Regarding adaptive immune cells, as well as T cells, both developing and mature B cells were detected, indicating that the lung environment supports B cell development.
The findings fundamentally change the understanding of immune and epithelial interactions that are crucial for fetal lung maturation. They also suggest that early immune disorders could manifest as pediatric lung disease.
This new knowledge on the mechanisms of early lung formation will also contribute to the development of new therapeutic approaches to regenerate damaged lung tissue and restore lung function.
Dr Peng He and Dr Jo Barnes, co-first authors of the study at EMBL's Wellcome Sanger Institute and European Bioinformatics Institute and UCL Division of Medicine respectively, said: “By adopting a targeted strategy in By mapping the immune system, we reveal a symbiotic relationship between immune cells and the developing lungs. This detailed information opens the door to potential regenerative therapies not only in the lung, but in other vital human organs.”
Dr Marko Nikolić, senior author of the study in the UCL Division of Medicine and honorary consultant in respiratory medicine, said: “We now know that immunoepithelial crosstalk is a feature of early lung development.” This vital basis for healthy lung development will help us understand what happens when lung development processes are interrupted, for example in premature births, which can lead to respiratory deficiencies.”
Dr Kerstin Meyer, senior author of the study at the Wellcome Sanger Institute, said: “The active participation of immune cells expands the possibilities for understanding and tackling lung-forming diseases. What is extremely interesting about this mechanism is that it could apply to other organ systems as well.”
Dr Sarah Teichmann, senior author of the study at the Wellcome Sanger Institute and co-founder of the Human Cell Atlas, said: “If we want to fully understand the root causes of disease, we need a comprehensive view of
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