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Unravelling gamma delta T cell emergence and responses in the uterus

Objective

Gamma delta (gd) T cells constitute a small proportion of blood lymphocytes, but are enriched at barrier sites, where they reside in close contact with epithelial cells. Their location at sites of pathogenic insult and cellular transformation, together with their ability to promptly respond to tissue alterations, places them in a central position in immune protection. We have shown that epithelial molecules direct the development of tissue-specific populations of gd T cells. Indeed, we have identified a role for epithelial-expressed butyrophilin-like (Btnl) proteins in driving the development of epidermal and intraepithelial gd T cells. Importantly, the requirement for Btnls is conserved in intestinal gd T cells in humans. In this project, we will focus on uterine gd T cells, which are arguably one of the least understood populations of gd T cells. These cells bear a specific, invariant T cell receptor, and are thought to become precommitted to an IL-17A-secreting programme during early ontogeny. In other tissues, these cells, termed gd17, can rapidly produce the pro-inflammatory cytokine IL-17A following infection, thereby contributing to limiting infection with bacterial and fungal pathogens. In addition, gd17 cells have been shown to play a role in tissue repair, including promotion of fracture repair. However, the inflammatory effects of IL-17A can also lead to exacerbation of tissue damage and to a pro-tumorigenic effect. In this project, we will determine the functional characteristics of uterine gd T cells, and identify novel factors guiding the development and homing of these cells. Understanding the cues driving gd T cell development and activation at specific body niches is not only essential from a basic research standpoint, but may reveal novel drug targets for various clinical conditions, particularly in the face of emerging infections targeting the female reproductive tract and hindering embryonic development.

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MSCA-IF-EF-ST - Standard EF

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2017

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Coordinator

THE FRANCIS CRICK INSTITUTE LIMITED
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 183 454,80
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Region
London Inner London — West Camden and City of London
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 183 454,80
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