Early human lung immune cell development and its role in epithelial cell fate

Studies of human lung development have focused on epithelial and mesenchymal cell types and function, but much less is known about the developing lung immune cells, even though the airways are a major site of mucosal immunity after birth. An unanswered question is whether tissue-resident immune cells play a role in shaping the tissue as it develops in utero. Here, we profiled human embryonic and fetal lung immune cells using scRNA-seq, smFISH, and immunohistochemistry. At the embryonic stage, we observed an early wave of innate immune cells, including innate lymphoid cells, natural killer cells, myeloid cells, and lineage progenitors. By the canalicular stage, we detected naive T lymphocytes expressing high levels of cytotoxicity genes and the presence of mature B lymphocytes, including B-1 cells. Our analysis suggests that fetal lungs provide a niche for full B cell maturation. Given the presence and diversity of immune cells during development, we also investigated their possible effect on epithelial maturation. We found that IL-1β drives epithelial progenitor exit from self-renewal and differentiation to basal cells in vitro. In vivo, IL-1β-producing myeloid cells were found throughout the lung and adjacent to epithelial tips, suggesting that immune cells may direct human lung epithelial development. With these novel results, we are the first - to the best of our knowledge - to show that immune cells have the ability to contribute to cell fate decisions during pre-natal human organ development. (Josephine L. Barnes et al., Sci. Immunol.8, 2023.)

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Published
2024-09-14
DOI
https://doi.org/10.1183/13993003.congress-2024.oa1893
Primary Topic
Neonatal Respiratory Health Research
Type
article
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article

Early human lung immune cell development and its role in epithelial cell fate

Kaylee B. Worlock, Iván T. Herczeg, Zewen Kelvin Tuong, Dawei Sun et al.
Neonatal Respiratory Health Research
article

Early human lung immune cell development and its role in epithelial cell fate

Kaylee B. Worlock, Iván T. Herczeg, Zewen Kelvin Tuong, Dawei Sun, Anna Wilbrey-Clark, Lira Mamanova, Chenqu Suo, J. Patrick Pett, Emma L. Rawlins, Rik G.H. Lindeboom, Marko Nikolić, Robert E. Hynds, John C. Marioni, Josephine L. Barnes, Paul Lyons, Sarah Teichmann, Adam Pennycuick, Kyungtae Lim, Sam M. Janes, Muzlifah A. Haniffa, Masahiro Yoshida, Laura Richardson, A.L. Oliver, Menna Ruth Clatworthy, Christiana Ruhrberg, Emma Dann, James L. Reading, Krzysztof Polański, Romina Arzili, Peng He, Kerstin B. Meyer, V. Teixeira, Jessica Allen-Hytinnen
article en

Abstract

Studies of human lung development have focused on epithelial and mesenchymal cell types and function, but much less is known about the developing lung immune cells, even though the airways are a major site of mucosal immunity after birth. An unanswered question is whether tissue-resident immune cells play a role in shaping the tissue as it develops in utero. Here, we profiled human embryonic and fetal lung immune cells using scRNA-seq, smFISH, and immunohistochemistry. At the embryonic stage, we observed an early wave of innate immune cells, including innate lymphoid cells, natural killer cells, myeloid cells, and lineage progenitors. By the canalicular stage, we detected naive T lymphocytes expressing high levels of cytotoxicity genes and the presence of mature B lymphocytes, including B-1 cells. Our analysis suggests that fetal lungs provide a niche for full B cell maturation. Given the presence and diversity of immune cells during development, we also investigated their possible effect on epithelial maturation. We found that IL-1β drives epithelial progenitor exit from self-renewal and differentiation to basal cells in vitro. In vivo, IL-1β-producing myeloid cells were found throughout the lung and adjacent to epithelial tips, suggesting that immune cells may direct human lung epithelial development. With these novel results, we are the first - to the best of our knowledge - to show that immune cells have the ability to contribute to cell fate decisions during pre-natal human organ development. (Josephine L. Barnes et al., Sci. Immunol.8, 2023.)

Broad Institute (US), University of Seoul (KR), The University of Queensland (AU), Korea University (KR), University of Cambridge (GB), The Gurdon Institute (GB), Wellcome Sanger Institute (GB), The Netherlands Cancer Institute (NL), Tokyo Zokei University (JP), Bioinformatics Institute (RU), Genomics England (GB), CRUK Lung Cancer Centre of Excellence (GB), Genomics (United Kingdom) (GB), Korea University (JP), University College London (GB), Newcastle University (GB)
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