Projects per year
Abstract / Description of output
Alveolar macrophages are the most abundant macrophages in the healthy lung where they play key roles in homeostasis and immune surveillance against air-borne pathogens. Tissue-specific differentiation and survival of alveolar macrophages relies on niche-derived factors, such as granulocyte-macrophage colony stimulating factor 2 (GM-CSF) and transforming growth factor beta (TGF-). However, the nature of the downstream molecular pathways that regulate the identity and function of alveolar macrophages and their response to injury remains poorly understood. Here, we identify that the transcriptional factor EGR2 is an evolutionarily conserved feature of lung alveolar macrophages and show that cell-intrinsic EGR2 is indispensable for the tissue-specific identity of alveolar macrophages. Mechanistically, we show that EGR2 is driven by TGF- and GM-CSF in a PPAR--dependent manner to control alveolar macrophage differentiation. Functionally, EGR2 was dispensable for regulation of lipids in the airways, but crucial for the effective handling of the respiratory pathogen Streptococcus pneumoniae. Finally, we show that EGR2 is required for repopulation of the alveolar niche following sterile, bleomycin-induced lung injury and demonstrate that EGR2-dependent, monocyte-derived alveolar macrophages are vital for effective tissue repair following injury. Collectively, we demonstrate that EGR2 is an indispensable component of the transcriptional network controlling the identity and function of alveolar macrophages in health and disease.
Original language | English |
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Journal | Science Immunology |
Volume | 6 |
Issue number | 65 |
DOIs | |
Publication status | Published - 19 Nov 2021 |
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Dive into the research topics of 'The transcription factor EGR2 is indispensable for tissue-specific imprinting of alveolar macrophages in health and tissue repair'. Together they form a unique fingerprint.Projects
- 4 Finished
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Decoding macrophage functional heterogeneity in the pathogenesis of Crohn's disease
1/10/20 → 30/09/24
Project: Research
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Defining the interplay between hypoxia and metabolic adaptations of the innate immune response.
1/01/18 → 31/12/22
Project: Research
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Investigating the role of TGF¿¿ in the functional imprinting of pulmonary macrophages in health and disease
1/09/17 → 31/12/23
Project: Research
Equipment
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Institute for Regeneration and Repair Flow Cytometry Facility
Shonna Johnston (Manager), Fiona Rossi (Manager), Claire Cryer (Other) & Ailsa Laird (Other)
Institute of Regeneration and RepairFacility/equipment: Facility