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Publication : Creatine transport and creatine kinase activity is required for CD8<sup>+</sup> T cell immunity.

First Author  Samborska B Year  2022
Journal  Cell Rep Volume  38
Issue  9 Pages  110446
PubMed ID  35235777 Mgi Jnum  J:324841
Mgi Id  MGI:7281932 Doi  10.1016/j.celrep.2022.110446
Citation  Samborska B, et al. (2022) Creatine transport and creatine kinase activity is required for CD8(+) T cell immunity. Cell Rep 38(9):110446
abstractText  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.
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