Periodic Reporting for period 1 - UTERUS (Unravelling gamma delta T cell emergence and responses in the uterus)
Reporting period: 2018-03-01 to 2020-02-29
This project sought to elucidate the biology of uterine gd T cells, one of the least understood populations of gd T cells. For example, their spatial and temporal location relative to the uterine epithelium and stroma are ill-defined. Moreover, there is little understanding of T cells more generally in the reproductive tract, a site highly vulnerable to infection and malignant transformation, and a common focus of medical intervention.
In this context the overarching goals for this project were:
1- To characterize and define the function of uterine gd T cells. In this aim, we determined the precise tissue localisation, dynamics and functional properties of uterine gd T cells.
2- To identify the endogenous and environmental mechanisms regulating uterine gd T cells. In this aim, we sought to identify and characterise candidate molecules that regulate the development and/or maintenance of uterine gd T cells, asking whether they act via generalisable mechanisms in common with skin and gut gd T cells, or whether they are unique. Additionally, we studied whether the microbiome regulates the development and/or function of uterine gd T cells, as has been claimed to be the case for some other gd T cell compartments.
Our data have generated the most comprehensive analysis to date of gd T cells in the murine uterus, highlighting their localisation within the uterine stroma and their population kinetics. We have also shown that the cells express a set of characteristic molecules, among which is the proinflammatory mediator IL-17A, which is associated with protection against fungal infections. Indeed, despite being dispensable for normal pregnancy, gd T cells played a critical role in protection of the female reproductive tract against Candida albicans infection.
Results from this project were presented as posters and oral presentations at various regional and international conferences, including the 8th international gd T cell conference in Bordeaux in 2018, the ThymE T cell and Thymus Biology conference in Israel in 2019, the Mucosal Immunology Conference in Australia in 2019 and the British Society for Immunology (BSI) annual conference in 2019. Furthermore, the data was presented in internal Crick and King’s College seminars, and as part of our weekly lab meeting which provided productive feedback for the project.
Our findings from this project were submitted for publication to Mucosal Immunology in October 2019, and received favourable reviews. All experiments requested by the reviewers were completed and a revised manuscript was resubmitted in April 2020. In addition, the initial UTERUS project has led to the initiation of two additional research projects, which we estimate will be ready for submission at the end of 2020/beginning of 2021. In addition to these research papers, in 2019, Dr. Monin co-authored a review article in Immunology titled “Immune responses in the human female reproductive tract”.
Furthermore, we were able to communicate our research objectives from the UTERUS project to a variety of audiences through participation in several outreach and teaching activities, which included a Genetic Engineering practical workshop organised by the public engagement team at the Crick; a Medicine at the Crick course organised by UCL; and an outreach activity to school children aged 4-5.