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. |