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Alveolar macrophages strictly rely on GM-CSF from alveolar epithelial type 2 cells before and after birth

View ORCID ProfileJulia Gschwend, View ORCID ProfileSamantha Sherman, Frederike Ridder, View ORCID ProfileXiaogang Feng, View ORCID ProfileHong-Erh Liang, View ORCID ProfileRichard M. Locksley, View ORCID ProfileBurkhard Becher, View ORCID ProfileChristoph Schneider
doi: https://doi.org/10.1101/2021.04.01.438051
Julia Gschwend
1Institute of Physiology, University of Zurich, Switzerland
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Samantha Sherman
1Institute of Physiology, University of Zurich, Switzerland
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Frederike Ridder
2Institute of Experimental Immunology, University of Zurich, Switzerland
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Xiaogang Feng
1Institute of Physiology, University of Zurich, Switzerland
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Hong-Erh Liang
3Department of Medicine, University of California San Francisco, San Francisco, California 94143-0795, USA
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Richard M. Locksley
3Department of Medicine, University of California San Francisco, San Francisco, California 94143-0795, USA
4Department of Microbiology & Immunology, University of California San Francisco, San Francisco, California 94143-0552, USA
5Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California
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Burkhard Becher
2Institute of Experimental Immunology, University of Zurich, Switzerland
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Christoph Schneider
1Institute of Physiology, University of Zurich, Switzerland
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  • For correspondence: christoph.schneider@uzh.ch
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ABSTRACT

Programs defining tissue-resident macrophage identity depend on local environmental cues. For alveolar macrophages (AMs), these signals are provided by immune and non-immune cells, and include GM-CSF (CSF2). However, evidence to functionally link components of this intercellular crosstalk remains scarce. We thus developed new transgenic mice to profile pulmonary GM-CSF expression, which we detected in both immune cells, including group 2 innate lymphoid cells and γδ T cells, as well as AT2s. AMs were unaffected by constitutive deletion of hematopoietic Csf2 and basophil depletion. Instead, AT2 lineage-specific constitutive and inducible Csf2 deletion revealed the non-redundant function of AT2-derived GM-CSF in instructing AM fate, establishing the postnatal AM compartment, and maintaining AMs in adult lungs. This AT2-AM relationship begins during embryogenesis, where nascent AT2s timely induce GM-CSF expression to support the proliferation and differentiation of fetal monocytes contemporaneously seeding the tissue, and persists into adulthood, when epithelial GM-CSF remains restricted to AT2s.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted April 03, 2021.
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Alveolar macrophages strictly rely on GM-CSF from alveolar epithelial type 2 cells before and after birth
Julia Gschwend, Samantha Sherman, Frederike Ridder, Xiaogang Feng, Hong-Erh Liang, Richard M. Locksley, Burkhard Becher, Christoph Schneider
bioRxiv 2021.04.01.438051; doi: https://doi.org/10.1101/2021.04.01.438051
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Alveolar macrophages strictly rely on GM-CSF from alveolar epithelial type 2 cells before and after birth
Julia Gschwend, Samantha Sherman, Frederike Ridder, Xiaogang Feng, Hong-Erh Liang, Richard M. Locksley, Burkhard Becher, Christoph Schneider
bioRxiv 2021.04.01.438051; doi: https://doi.org/10.1101/2021.04.01.438051

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