Research show immune cells shape lungs tissue before birth

Research Reveals Immune Cells Play Vital Role in Early Lung Development, Paving the Way for New Respiratory Disease Treatments

by Wellcome Trust Sanger Institute

A groundbreaking study conducted by researchers at the Wellcome Sanger Institute and University College London (UCL) has unveiled the active involvement of immune cells in shaping human lung tissue during fetal development. This discovery revolutionizes our understanding of early lung development and challenges the conventional perception of immune cells solely within the realm of immunity.

The findings of this research hold immense potential for advancing the understanding and treatment of respiratory conditions, particularly chronic obstructive pulmonary disease (COPD), which accounts for nearly 20% of all childhood deaths worldwide.

Unlike previous notions, this study establishes a remarkable coordination between the immune and respiratory systems even earlier in the developmental process. The implications of this revelation extend to other developing organs, prompting further investigation into the role of immune cells.

In order to map the development of early human lung immune cells over time, the research team employed sophisticated single-cell technologies. Their work has resulted in the creation of an unprecedented immune cell atlas specifically for the developing lung. This collaboration is part of the larger international Human Cell Atlas initiative, aimed at comprehensively mapping every cell type in the human body to transform our understanding of health, infection, and disease.

Published in the journal Science Immunology, the study sheds light on the mechanisms underlying childhood lung diseases, ultimately contributing to more effective treatments.

While immune cells are known to constitute a significant portion of mature lungs and airways, responsible for crucial gas exchange and barrier functions, their roles in early organ development have remained unexplored. Recent discoveries have revealed the presence of immune cells in human lungs as early as five weeks into development.

To examine whether the immune system influences lung growth, the researchers studied immune cells in early human lungs ranging from 5 to 22 weeks. Utilizing various techniques, such as single-cell sequencing and experiments with lung cell cultures, they sought to determine if immune cells could impact lung cell development.

The study identified key regulators of lung development, notably IL-1β and IL-13 signaling molecules, which facilitate the coordination of lung stem cells differentiating into specialized mature cell types.

The researchers observed the infiltration of innate immune cells followed by adaptive immune cells. Innate cells identified included innate lymphoid cells (ILCs), natural killer (NK) cells, myeloid cells, and progenitor cells. In terms of adaptive immune cells, both developing and mature B lineage cells were detected, indicating that the lung environment supports B cell development.

These findings fundamentally transform our understanding of the immune and epithelial interactions critical to the maturation of fetal lungs. They also suggest that disruptions in immune function during early development may lead to pediatric lung diseases.

Moreover, the insights gained into early lung formation mechanisms will drive the development of novel therapeutic approaches for regenerating damaged lung tissue and restoring lung function.

Co-first authors of the study, Dr. Peng He and Dr. Jo Barnes from the Wellcome Sanger Institute, and EMBL's European Bioinformatics Institute, and UCL Division of Medicine, expressed their excitement about the discovered symbiotic relationship between immune cells and developing lungs. They believe that these detailed insights pave the way for potential regenerative therapies not only in the lung but also in other crucial human organs.

Dr. Marko Nikolić, senior author of the study from UCL Division of Medicine and honorary consultant in respiratory medicine, emphasized the significance of immune-epithelial crosstalk in early lung development. Understanding the implications of disruptions in lung developmental processes, such as those occurring in preterm births, is vital to addressing respiratory deficiencies.

Dr. Kerstin Meyer, senior author of the study at the Wellcome Sanger Institute, remarked on the active participation of immune cells, stressing the potential for gaining a deeper understanding of impaired lung formation. She also hinted at the possibility of applying this mechanism to other organ systems, evoking excitement about potential future discoveries.

Finally, Dr. Sarah Teichmann, senior author of the study at the Wellcome Sanger Institute and Co-founder of the Human Cell Atlas, emphasized the necessity of a comprehensive view of cells at all stages in the human body to fully comprehend the root causes of disease. This study's groundbreaking contribution to the Human Cell Atlas serves as a valuable reference for studying lung diseases extensively.

This article is based on research conducted by the Wellcome Trust Sanger Institute and University College London (UCL). The original article can be accessed medicaexpresshttps ://medicalxpress.com/news/2023-12-immune-cells-lung-tissue-birth.html