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Metabolic imprinting of Th17 cells in disease pathogenesis

Projektbeschreibung

Pathogenese von Autoimmunerkrankungen und metabolische Prägung von CD4+T-Zellen

Die Wissenschaft hat rund 80 Autoimmunerkrankungen ermittelt, von denen bis zu 9 % der Weltbevölkerung betroffen sind. Die IL-17-produzierenden CD4+T-Zellen (Th17) sind über die Rekrutierung in entzündetem Gewebe an der Autoimmunpathogenese beteiligt. Die Th17-Zellen unterscheiden sich in verschiedenen Geweben in ihrer Transkription, und Stoffwechselmanipulationen wirken sich auf die Th17-Zellen aus. Das über die Marie-Skłodowska-Curie-Maßnahmen finanzierte Projekt Th17 tissue metab wird die Einzelzell-RNS-Sequenzierung und innovative Stoffwechselanalysewerkzeuge nutzen, um einen Gewebestoffwechselschalter für die Pathogenität von Th17-Zellen festzustellen und die Hypothese zu überprüfen, dass metabolische Hinweise aus dem Zielgewebe den Th17-Phänotyp bestimmen. Die Ergebnisse dieser Analyse werden anhand eines Mausmodells für Autoimmunerkrankungen der Multiplen Sklerose weiter validiert.

Ziel

Autoimmune diseases affect an estimated 3-9% of the population and cause major personal and socio-economic consequences. IL-17-producing CD4+ T cells (Th17) are recruited to inflamed tissues and involved in autoimmune pathogenesis but were recently also shown to have homeostatic function in tissues. Preliminary data from the outgoing host indicate that Th17 cells are transcriptionally distinct in different tissues. How tissue Th17 cells acquire such specialized characteristics remains elusive. Based on recent findings from the lab that a metabolic manipulation affects Th17 cells, we hypothesize that metabolic cues from the target tissue dictate Th17 phenotypes. To address this, we will apply scRNAseq and the host lab developed Compass metabolic flux tool in 9 tissues. Hits from this analysis will undergo a novel screening approach, CHIME, to reveal effects on Th17 function. In autoimmunity, Th17 cells reside within different tissues before migrating to the inflamed tissue. Identifying a tissue metabolic switch for Th17 cell pathogenicity might thus pave the way for novel treatments. To study this, I will use a mouse model for the autoimmune disease multiple sclerosis (MS) for target validation. During the return phase, the findings will be set into context of tissue niche immunology and human biology. In healthy versus inflamed human tissue, spatial RNAseq will directly reveal metabolism related differences in a natural tissue niche context. The project will be performed in a world-renowned Th17 lab. The fellow brings extensive experience with tissue immune cell extractions and MS mouse models, enabling immediate project progression. The fellow will then bring back novel techniques and experience (scRNAseq, CHIME) to the return host, where she will acquire skills in human tissue niche immunology and spatial RNAseq. This project will enhance her expertise, research and transferable skills and allow to build a network to follow her goal of becoming an independent PI.

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Koordinator

JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG
Netto-EU-Beitrag
€ 265 647,84
Adresse
Sanderring 2
97070 Wuerzburg
Deutschland

Auf der Karte ansehen

Region
Bayern Unterfranken Würzburg, Kreisfreie Stadt
Aktivitätstyp
Higher or Secondary Education Establishments
Links
EU-Beitrag
Keine Daten

Partner (1)