Creatine transport and creatine kinase activity is required for CD8 + T cell immunity.

Autor:	Samborska B; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada., Roy DG; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada., Rahbani JF; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada., Hussain MF; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada., Ma EH; Department of Metabolism and Nutritional Programming, Van Andel Research Institute, Grand Rapids, MI 49503, USA., Jones RG; Department of Metabolism and Nutritional Programming, Van Andel Research Institute, Grand Rapids, MI 49503, USA., Kazak L; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada. Electronic address: lawrence.kazak@mcgill.ca.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 Mar 01; Vol. 38 (9), pp. 110446.
DOI:	10.1016/j.celrep.2022.110446
Abstrakt:	The factors that promote T cell expansion are not fully known. Creatine is an abundant circulating metabolite that has recently been implicated in T cell function; however, its cell-autonomous role in immune-cell function is unknown. Here, we show that creatine supports cell-intrinsic CD8 + T cell homeostasis. We further identify creatine kinase B (CKB) as the creatine kinase isoenzyme that supports these T cell properties. Loss of the creatine transporter (Slc6a8) or Ckb results in compromised CD8 + T cell expansion in response to infection without influencing adenylate energy charge. Rather, loss of Slc6a8 or Ckb disrupts naive T cell homeostasis and weakens TCR-mediated activation of mechanistic target of rapamycin complex 1 (mTORC1) signaling required for CD8 + T cell expansion. These data demonstrate a cell-intrinsic role for creatine transport and creatine transphosphorylation, independent of their effects on global cellular energy charge, in supporting CD8 + T cell homeostasis and effector function. Competing Interests: Declaration of interests R.G.J. is a consultant for Agios Pharmaceuticals and Servier Pharmaceuticals and serves on the Scientific Advisory Board of ImmunoMet Therapeutics. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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