Lung development “atlas” opens the way for new treatments

British scientists have announced the first-of-its-kind immune cell atlas of the developing lung.

The finding fundamentally alters previous understanding of early lung development and provides new insights for understanding and treating respiratory conditions, such as chronic obstructive pulmonary disease (COPD), according to researchers.

Researchers from the Wellcome Sanger Institute, University College London (UCL) and EMBL’s European Bioinformatics Institute used advanced single-cell technologies to map the development of early human lung immune cells over time.

They revealed a surprising coordination between the immune and respiratory systems, happening much earlier in development than previously thought.

Writing in Science Immunology, the researchers say this raises questions about the potential role of immune cells in other developing organs across the body.

The roles of immune cells in the developing organ have remained unexplored compared to structural or lining cell types, so to explore if the immune system influence how 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 if immune cells could affect lung cell development, and identified key regulators of lung development. These included signalling molecule IL-1β and IL-13 that facilitate the coordination of lung stem cells differentiating into specialised mature cell types.

The researchers identified an infiltration of innate, followed by adaptive immune cells, which included innate lymphoid cells (ILCs), natural killer (NK) cells, myeloid cells and progenitor cells.

They found developing and mature B lineage cells in adaptive immune cells and T cells, indicating that the lung environment supports B cell development.

This changes the understanding of the immune and epithelial interactions that are crucial for foetal lung maturation and the researchers suggest it may mean early immune disturbances could manifest as paediatric lung disease.

First study authors Dr Peng He and Dr Jo Barnes, of the Wellcome Sanger Institute and EMBL’s European Bioinformatics Institute, and UCL Division of Medicine respectively, said: “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.”

Dr Marko Nikolić, senior author from UCL Division of Medicine, added: “We now know immune-epithelial crosstalk is a feature of early lung development. 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.”

Barnes JLL et al. Early human lung immune cell development and its role in epithelial cell fate. Science Immunology 15 December 2023; DOI: 10.1126/sciimmunol.adf9988


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