Descrizione del progetto
Cellule T regolatrici residenti nei reni in condizioni di salute e di malattia
I pazienti affetti da malattia renale cronica o allo stadio terminale spesso ricorrono al trapianto dei reni come rimedio. Le cellule T regolatrici (Regulatory T cells, Treg) sono state proposte come mezzo per indurre la tolleranza tessuto-specifica come alternativa alla soppressione immunitaria sistemica in seguito al trapianto. Al tempo stesso, tali cellule proteggono dalle lesioni e promuovono la riparazione dei tessuti. Tuttavia, non è ancora chiaro se questo effetto sia mediato dalle Treg residenti nei tessuti o da quelle in circolazione. Il progetto Kidney-Treg, finanziato dall’UE, caratterizzerà le Treg nel rene utilizzando tecniche di biologia molecolare d’avanguardia e stabilirà il loro impatto sulla fisiologia dei reni. L’obiettivo principale è quello di esplorare le funzioni di queste cellule residenti nei reni come nuovi strumenti terapeutici.
Obiettivo
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.
Campo scientifico
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Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
CB22 3AT Cambridge
Regno Unito