Macrophage-epithelial communication promotes lung repair after injury (360G-Wellcome-206566_Z_17_Z)
Lung epithelial injury is the near-universal sequela of multiple pulmonary insults. Rapid restoration of mucosal integrity prevents impaired gas exchange and superadded bacterial infection, but aberrant tissue repair is a frequent, often fatal, outcome in disease. Despite this, no current treatments target homeostatic repair processes. Macrophages are pivotal for efficient tissue repair but how they communicate with epithelium to achieve this remains poorly understood. During injury, macrophage engulfment of apoptotic cells or exposure to inflammation-associated cytokines leads them to release extracellular vesicles (microvesicles) and insulin-like growth factor-1 (IGF-1). IGF-1 inhibits epithelial engulfment of apoptotic cells but enhances epithelial microvesicle uptake. Furthermore, increased leukocyte-derived microvesicles and elevated IGF-1 correlate with improved patient survival from lung injury, suggesting this macrophage-epithelial communication system may deliver key anti-inflammatory, pro-reparative signals. Indeed, macrophages release extracellular factors that enhance epithelial proliferation (integral to repair) and proliferation is reduced by attenuating epithelial microvesicle uptake. My central hypothesis is that lung macrophage-epithelial communication is enhanced following lung injury and promotes repair. My key aims are to investigate: How macrophage-derived signals influence lung epithelial responses Mechanisms governing lung epithelial uptake of microvesicles Signals delivered by macrophage microvesicles to epithelium, and whether they promote repair after injury
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Grant Details
Amount Awarded | 770022 |
Applicant Surname | Lucas |
Approval Committee | Clinical Interview Committee |
Award Date | 2017-05-25T00:00:00+00:00 |
Financial Year | 2016/17 |
Grant Programme: Title | Clinical Research Career Development Fellowship |
Internal ID | 206566/Z/17/Z |
Lead Applicant | Dr Christopher Lucas |
Partnership Value | 770022 |
Planned Dates: End Date | 2022-08-04T00:00:00+00:00 |
Planned Dates: Start Date | 2017-07-03T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Scotland |
Sponsor(s) | Prof Adriano Rossi |