期刊
NATURE IMMUNOLOGY
卷 20, 期 5, 页码 571-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41590-019-0352-y
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资金
- MCCIR PhD studentship
- Medical Research Council [MR/P026907/1]
- National Institutes of Health [HL080396, HL130938]
- Wellcome Trust Institutional Strategic Support Fund [105610]
- Medical Research Foundation UK
- Asthma UK [MRFAUK-2015-302]
- University of Manchester Dean's Prize Early Career Research Fellowship
- Springboard Award (Academy of Medical Sciences) [SBF002/1076]
- MCCIR
- Wellcome Trust [097820/Z/11/B]
- BBSRC
- University of Manchester Strategic Fund
- Wellcome Trust [097820/Z/11/B] Funding Source: Wellcome Trust
Fine control of macrophage activation is needed to prevent inflammatory disease, particularly at barrier sites such as the lungs. However, the dominant mechanisms that regulate the activation of pulmonary macrophages during inflammation are poorly understood. We found that alveolar macrophages (AlvMs) were much less able to respond to the canonical type 2 cytokine IL-4, which underpins allergic disease and parasitic worm infections, than macrophages from lung tissue or the peritoneal cavity. We found that the hyporesponsiveness of AlvMs to IL-4 depended upon the lung environment but was independent of the host microbiota or the lung extracellular matrix components surfactant protein D (SP-D) and mucin 5b (Muc5b). AlvMs showed severely dysregulated metabolism relative to that of cavity macrophages. After removal from the lungs, AlvMs regained responsiveness to IL-4 in a glycolysis-dependent manner. Thus, impaired glycolysis in the pulmonary niche regulates AlvM responsiveness during type 2 inflammation.
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