Identifying novel biologically relevant interactions between lymph node stroma and innate immune cells. (360G-Wellcome-109783_Z_15_Z)

£97,579

Fibroblastic reticular cells (FRCs) reside in secondary lymphoid organs, where they strongly shape adaptive immunity. However, interactions with immunologically important macrophage and neutrophil populations are completely undescribed. I recently found the first evidence that FRCs directly induce monocyte differentiation, and that they attract macrophages then arrest their migration. Excitingly, I also found that FRCs express a gene signature highly relevant to macrophage and neutrophil influx and function, and that expression of key chemokines increases immediately (1h) after LPS exposure. As robust proof-of-principle, FRC depletion reduces macrophage numbers by 95% in lymph nodes. I therefore hypothesise that FRCs fundamentally regulate macrophages and neutrophils in secondary lymphoid organs. Robust demonstration that FRCs support the innate immune response will, I believe, be high impact if this project is developed. Goals: 1. To test FRC interactions with macrophages and neutrophils through co-culture and live cell imaging, developing relevant data that allows me to prove my abilities with innate immune cells. 2. To inhibit key factors produced by stroma, examining effects on macrophage and neutrophil migration, phenotype and function. 3. To use a targeted in vivo model of FRC depletion (FAP-DTR) to dissect FRC-mediated control of macrophages and neutrophil function.

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Grant Details

Amount Awarded 97579
Applicant Surname Fletcher
Approval Committee ERG4 Immune System in Health and Disease
Award Date 2015-09-11T00:00:00+00:00
Financial Year 2014/15
Grant Programme: Title Seed Award in Science
Internal ID 109783/Z/15/Z
Lead Applicant Dr Anne Fletcher
Partnership Value 97579
Planned Dates: End Date 2018-05-01T00:00:00+00:00
Planned Dates: Start Date 2016-03-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region West Midlands