Project description
Kidney-resident regulatory T cells in health and disease
Patients suffering from chronic or end-stage renal disease often resort to kidney transplantation as a cure. Regulatory T cells (Tregs) have been proposed as a means of inducing tissue-specific tolerance as an alternative to systemic immune suppression following transplantation. At the same time, they protect from injury and promote tissue repair. However, it is yet unclear whether this effect is mediated by tissue-resident Tregs or those in circulation. The EU-funded Kidney-Treg project will characterise Tregs in the kidney using state-of-the-art molecular biology techniques and determine their impact on kidney physiology. The key objective is to explore the functions of these kidney-resident cells as novel therapeutic tools.
Objective
Tregs are a subtype of T cells exerting immunosuppressive functions that are vital to prevent autoimmunity. Recently, tissue-resident Tregs have been proposed to be phenotypically and functionally distinct from the generic Tregs in circulation. Systemic Treg supplementation and depletion studies strongly support a role for Tregs in protection from injury and promotion of tissue repair in models of kidney diseases, highlighting the potential of harnessing Tregs in these pathologies. However, due to the systemic nature of the Treg manipulation in these studies, it is unknown if the effect resides in systemic impacts or in tissue-based impacts. The aim of this project is to characterise Tregs located in the kidney and to expand the kidney-resident Treg population, without impacting the systemic population, in order to evaluate their specific impact on the physiology and pathologies of the kidney. First, I will characterise the kidney-resident Tregs using state-of-the-art molecular biology techniques, such as scRNAseq, and an innovative mouse model of cell fate mapping based on a photoactivatable Cre-recombinase. Second, I will evaluate their specific functions in physiology and pathologies of the kidney using a mouse model of tissue-specific Treg expansion uniquely available in the host laboratory. As well as the novel biology exploring the potential functions of kidney-resident Tregs, the distinction between systemic and kidney-based effects is critical to develop new therapeutic tools aiming to target kidney-resident Tregs. The induction of tissue-specific tolerance for kidney autoimmunity or transplantation, without inducing systemic immune suppression, constitute a promising and feasible alternative to existing immunosuppressive therapies. The knowledge and experience gained from this project combined with my scientific and personal development will give me all the skills I need to achieve my objective to pursue an exciting scientific career in academia.
Fields of science
Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
CB22 3AT Cambridge
United Kingdom