@article{c6a5af1d934b4200bb1f81245f6635bd,
title = "Niche-Selective Inhibition of Pathogenic Th17 Cells by Targeting Metabolic Redundancy",
abstract = "Metabolic redundancy differs according to microenvironments, making the glycolysis gene Gpi1 dispensable for homeostatic Th17 cells in normal tissue but essential for pathogenic Th17 cells in hypoxic inflamed tissue.",
keywords = "CRISPR, EAE, OXPHOS, autoimmunity, colitis, glycolysis, hypoxia, inflammation, metabolic plasticity, segmented filamentous bacteria",
author = "Lin Wu and Hollinshead, {Kate E.R.} and Yuhan Hao and Christy Au and Lina Kroehling and Charles Ng and Lin, {Woan Yu} and Dayi Li and Silva, {Hernandez Moura} and Jong Shin and Lafaille, {Juan J.} and Richard Possemato and Pacold, {Michael E.} and Thales Papagiannakopoulos and Kimmelman, {Alec C.} and Rahul Satija and Littman, {Dan R.}",
note = "Funding Information: We thank the NYU Langone Genome Technology Center for expert library preparation and sequencing. This shared resource is partially supported by the Cancer Center Support Grant P30CA016087 at the Laura and Isaac Perlmutter Cancer Center . We thank Drew R. Jones and Rebecca E. Rose in the NYU Metabolomics Laboratory for helpful discussion and aid with LC-MS data generation and analysis. We thank S.Y. Kim in the NYU Rodent Genetic Engineering Laboratory (RGEL) for generating the Tpi1 conditional KO mice. We thank Anne R. Bresnick (Department of Biochemistry, Albert Einstein College of Medicine) for sharing the S100a4 mutant mice. This work was supported by National Multiple Sclerosis Society Fellowship FG 2089-A-1 (L.W.), Immunology and Inflammation training grant T32AI100853 (C.N.), NIH grant R01AI121436 (D.R.L.), the Howard Hughes Medical Institute (D.R.L.), and the Helen and Martin Kimmel Center for Biology and Medicine (D.R.L.) Funding Information: We thank the NYU Langone Genome Technology Center for expert library preparation and sequencing. This shared resource is partially supported by the Cancer Center Support Grant P30CA016087 at the Laura and Isaac Perlmutter Cancer Center. We thank Drew R. Jones and Rebecca E. Rose in the NYU Metabolomics Laboratory for helpful discussion and aid with LC-MS data generation and analysis. We thank S.Y. Kim in the NYU Rodent Genetic Engineering Laboratory (RGEL) for generating the Tpi1 conditional KO mice. We thank Anne R. Bresnick (Department of Biochemistry, Albert Einstein College of Medicine) for sharing the S100a4 mutant mice. This work was supported by National Multiple Sclerosis Society Fellowship FG 2089-A-1 (L.W.), Immunology and Inflammation training grant T32AI100853 (C.N.), NIH grant R01AI121436 (D.R.L.), the Howard Hughes Medical Institute (D.R.L.), and the Helen and Martin Kimmel Center for Biology and Medicine (D.R.L.), L.W. and D.R.L. conceived the project and wrote the manuscript. L.W. designed, performed experiments, and analyzed the data. L.W. and K.E.R.H. designed and performed the GC-MS flux, tracing, and seahorse experiments, and analyzed the data. Y.H. and R.S. analyzed the scRNA-seq data. L.K. analyzed the bulk RNA-seq data. C.A. W.-Y.L. D.L. and H.M.S. helped with mouse experiments. C.N. and W.-Y.L. helped with the development of the CRISPR/Cas9 transfection method. J.S. and R.P. helped with GC-MS experiments. K.E.R.H. J.J.L. R.P. M.E.P. T.P. and A.C.K. assisted with the analysis and interpretation of the metabolic data. K.E.R.H. H.M.S. S.J. J.J.L. R.P. M.E.P. T.P. A.C.K. and R.S. edited the manuscript. D.R.L. supervised the work. D.R.L. consults and has equity interest in Chemocentryx, Vedanta, and Pfizer Pharmaceuticals. The NYU School of Medicine has filed a provisional patent application related to this work. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = aug,
day = "6",
doi = "10.1016/j.cell.2020.06.014",
language = "English (US)",
volume = "182",
pages = "641--654.e20",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "3",
}