Project description DEENESFRITPL Autoimmune disease pathogenesis and metabolic imprinting of CD4+T cells Scientists identify around 80 autoimmune diseases that affect up to 9 % of the world's population. The IL-17-producing CD4+ T (Th17) cells are involved in autoimmune pathogenesis via recruitment to inflamed tissues. The Th17 cells are transcriptionally distinct in different tissues, and metabolic manipulation affects Th17 cells. Funded by the Marie Skłodowska-Curie Actions programme, the Th17 tissue metab project will use single-cell RNA sequencing and innovative metabolic analysis tools to identify a tissue metabolic switch for Th17 cell pathogenicity, testing the hypothesis that metabolic cues from the target tissue dictate Th17 phenotypes. The hits from this analysis will undergo further validation in a mouse autoimmune disease model for multiple sclerosis. Show the project objective Hide the project objective Objective 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. Fields of science medical and health sciencesbasic medicineneurologymultiple sclerosismedical and health sciencesbasic medicineimmunologyautoimmune diseases Programme(s) HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme Topic(s) HORIZON-MSCA-2021-PF-01-01 - MSCA Postdoctoral Fellowships 2021 Call for proposal HORIZON-MSCA-2021-PF-01 See other projects for this call Funding Scheme HORIZON-AG-UN - HORIZON Unit Grant Coordinator JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG Net EU contribution € 265 647,84 Address Sanderring 2 97070 Wuerzburg Germany See on map Region Bayern Unterfranken Würzburg, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window EU contribution No data Partners (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all BRIGHAM INC United States Net EU contribution € 0,00 Address Francis street 75 02115 Boston ma See on map Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding No data
