An international research group has utilized advanced single-cell technologies alongside studies in lung organoids to chart the development of early human lung immune cells. The results, unveiling an active and intimate role of immune cells in directing human lung tissue growth during development, challenge previous notions by revealing a surprising coordination between the immune and respiratory systems at an earlier stage than previously believed.
This groundbreaking study has produced a unique immune cell atlas of the developing lung, contributing to the international Human Cell Atlas initiative, aimed at mapping every cell type in the human body. The findings not only revolutionize our understanding of early lung development but also shed light on the role of immune cells beyond immunity. Moreover, they offer new perspectives on respiratory conditions like chronic obstructive pulmonary disease (COPD) and may provide insights into childhood lung diseases, prompting questions about the potential involvement of immune cells in the development of other organs in the body.
Dr. Kerstin Meyer from the Wellcome Sanger Institute highlighted the significance of immune cell involvement in lung formation, stating, “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.”
The study revealed that immune cells constitute a substantial portion of mature lungs, playing critical roles in gas exchange, barrier functions, and protection against respiratory infections. The research, spanning early human lung development from 5 to 22 weeks, utilized various techniques, including single-cell sequencing and 3D lung epithelial organoid cultures.
Infiltration of both innate and adaptive immune cells was observed, with innate cells including innate lymphoid cells, natural killer cells, myeloid cells, and progenitor cells. Developing and mature B lineage cells were also detected alongside T cells. The study identified key regulators of lung development, such as cytokine signaling molecules IL-1β and IL-13, facilitating the coordination of lung stem cells differentiating into mature cell types.
Remarkably, the study found that IL-1β, produced by immune cells, directly induced airway epithelial progenitor cells to differentiate into mature lung lining cells, providing critical insights into the immune-epithelial interactions crucial for fetal lung maturation. The findings suggest that early disturbances in the immune system could manifest as pediatric lung diseases, a significant contributor to global child mortality.
These insights into early lung formation mechanisms have potential implications for developing therapeutic approaches to regenerate damaged lung tissue and restore lung function. The researchers emphasized that their study lays the foundation for future functional analyses, offering a comprehensive understanding of the intricate interplay among immune, endothelial, epithelial, and mesenchymal cells in lung development.