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  Pharmacological Activation of Pyruvate Kinase M2 Inhibits CD4+-T Cell Pathogenicity and Suppresses Autoimmunity

Angiari, S., Runtsch, M. C., Sutton, C. E., Palsson-McDermott, E. M., Kelly, B., Rana, N., et al. (2020). Pharmacological Activation of Pyruvate Kinase M2 Inhibits CD4+-T Cell Pathogenicity and Suppresses Autoimmunity. Cell Metabolism, 31, 391-405. doi:org/10.1016/j.cmet.2019.10.015.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0006-3C98-C Version Permalink: http://hdl.handle.net/21.11116/0000-0006-3C99-B
Genre: Journal Article

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Angiari et al..pdf (Publisher version), 6MB
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2019
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 Creators:
Angiari, Stefano1, Author
Runtsch, Marah C.1, Author
Sutton, Caroline E.1, Author
Palsson-McDermott, Eva M.1, Author
Kelly, Beth1, Author
Rana, Nisha1, Author
Kane, Harry1, Author
Papadopoulou, Gina1, Author
Pearce, Erika L.2, Author              
Mills, Kingston H.G.1, Author
O'Neill, Luke A.J.1, Author
Affiliations:
1External Organizations, ou_persistent22              
2Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243648              

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 Abstract: Pyruvate kinase (PK) catalyzes the conversion of phosphoenolpyruvate to pyruvate during glycolysis. The PK isoform PKM2 has additional roles in regulation of gene transcription and protein phosphorylation. PKM2 has been shown to control macrophage metabolic remodeling in inflammation, but its role in T cell biology is poorly understood. Here, we report PKM2 upregulation, phosphorylation, and nuclear accumulation in murine and human CD4+ T cells following activation in vitro. Treatment of T cells with TEPP-46, an allosteric activator that induces PKM2 tetramerization and blocks its nuclear translocation, strongly reduces their activation, proliferation, and cytokine production by inhibiting essential signaling pathways and thus preventing the engagement of glycolysis. TEPP-46 limits the development of both T helper 17 (Th17) and Th1 cells in vitro and ameliorates experimental autoimmune encephalomyelitis (EAE) in vivo. Overall, our results suggest that pharmacological targeting of PKM2 may represent a valuable therapeutic approach in T cell-mediated inflammation and autoimmunity.

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Language(s): eng - English
 Dates: 2020-02-04
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: org/10.1016/j.cmet.2019.10.015
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Title: Cell Metabolism
  Other : Cell Metabolism
Source Genre: Journal
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Publ. Info: Cambridge, MA : Cell Press
Pages: - Volume / Issue: 31 Sequence Number: - Start / End Page: 391 - 405 Identifier: ISSN: 1550-4131
CoNE: https://pure.mpg.de/cone/journals/resource/111088195284928