Alveolar macrophages rely on GM-CSF from alveolar epithelial type 2 cells before and after birth
| Autor: | Burkhard Becher, Hong-Erh Liang, Christoph Schneider, Samantha P M Sherman, Frederike Ridder, Xiaogang Feng, Richard M. Locksley, Julia Gschwend |
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| Přispěvatelé: | University of Zurich, Schneider, Christoph |
| Rok vydání: | 2021 |
| Předmět: |
2700 General Medicine
Basophil 10263 Institute of Experimental Immunology Inbred C57BL Medical and Health Sciences Transgenic 10052 Institute of Physiology Mice 0302 clinical medicine Immunology and Allergy Macrophage Innate 2.1 Biological and endogenous factors Developmental Aetiology Lung Mice Knockout 0303 health sciences Innate lymphoid cell Gene Expression Regulation Developmental Cell Differentiation Cell biology Haematopoiesis Granulocyte macrophage colony-stimulating factor medicine.anatomical_structure Cytokines Stem Cell Research - Nonembryonic - Non-Human Female medicine.drug Genetically modified mouse Knockout Immunology 610 Medicine & health Mice Transgenic Biology Alveolar 03 medical and health sciences Immune system Macrophages Alveolar medicine Animals 030304 developmental biology Macrophages Immunity Granulocyte-Macrophage Colony-Stimulating Factor Epithelial Cells Newborn Stem Cell Research Immunity Innate Mice Inbred C57BL Gene Expression Regulation Animals Newborn 570 Life sciences biology 030217 neurology & neurosurgery |
| Zdroj: | The Journal of experimental medicine, vol 218, iss 10 |
| ISSN: | 1540-9538 |
| Popis: | Programs defining tissue-resident macrophage identity depend on local environmental cues. For alveolar macrophages (AMs), these signals are provided by immune and nonimmune cells and include GM-CSF (CSF2). However, evidence to functionally link components of this intercellular cross talk 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 nonredundant 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. |
| Databáze: | OpenAIRE |
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