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

Lookup NU author(s): Professor Muzlifah Haniffa, Dr Amanda Oliver

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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.

Publication metadata

Author(s): Barnes JL, Yoshida M, He P, Worlock KB, Lindeboom RGH, Suo C, Pett JP, Wilbrey-Clark A, Dann E, Mamanova L, Richardson L, Polanski K, Pennycuick A, Allen-Hyttinen J, Herczeg IT, Arzili R, Hynds RE, Teixeira VH, Haniffa M, Lim K, Sun D, Rawlins EL, Oliver AJ, Lyons PA, Marioni JC, Ruhrberg C, Tuong ZK, Clatworthy MR, Reading JL, Janes SM, Teichmann SA, Meyer KB, Nikolic MZ

Publication type: Article

Publication status: Published

Journal: Science Immunology

Year: 2023

Volume: 8

Issue: 90

Online publication date: 15/12/2023

Acceptance date: 03/11/2023

ISSN (electronic): 2470-9468

Publisher: American Association for the Advancement of Science (AAAS)

URL: https://doi.org/10.1126/sciimmunol.adf9988

DOI: 10.1126/sciimmunol.adf9988

PubMed id: 38100545

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