Differences in metabolic flux between non-pathogenic and pathogenic Th17 cells 3357

Abstract Description With the advancement of single cell sequencing technology, researchers have been able to identify and metabolically target a new subset of T-helper 17 (Th17) cells in mice: non-pathogenic (NP Th17) and pathogenic (P Th17) cells. The growing nuances of NP Th17 and P Th17 cells have been influential in understanding autoimmune disorders inflicted with chronic inflammation that is predominantly driven by Th17 cells. However, it is unclear whether these subsets of Th17 cells are present in and can also be metabolically targeted in humans, and in the context of other Th17 inflammatory dominated diseases, like type 2 diabetes (T2D). Previous studies have revealed that CD4+ T cells from T2D patients have decreased fatty acid/beta oxidation. Blocking beta oxidation in healthy T cells induced production of Th17-associated cytokines similar to T2D patients. Our lab has transcriptomically identified the presence and metabolic differences of human NP and P Th17 cells through novel enrichment methods and comparison to in-vitro differentiated Th17 cells. We have been able to validate these metabolic differences through a proteomic, flow cytometry based method called SCENITH that measures metabolic flux and dependencies. SCENITH has revealed metabolic flux differences between in-vitro differentiated NP and P Th17 cells. Identifying the differences in metabolic flux between the two subsets of Th17 cells enables to uncover potential therapeutic targets for treating T2D. Funding Sources NIH DP2AI171121-03S2 Topic Categories Mucosal and Regional Immunology (MUC)