| First Author | Edwards-Hicks J | Year | 2023 |
| Journal | Nat Immunol | Volume | 24 |
| Issue | 3 | Pages | 516-530 |
| PubMed ID | 36732424 | Mgi Jnum | J:350289 |
| Mgi Id | MGI:7662492 | Doi | 10.1038/s41590-023-01419-y |
| Citation | Edwards-Hicks J, et al. (2023) Phosphoinositide acyl chain saturation drives CD8(+) effector T cell signaling and function. Nat Immunol 24(3):516-530 |
| abstractText | How lipidome changes support CD8(+) effector T (T(eff)) cell differentiation is not well understood. Here we show that, although naive T cells are rich in polyunsaturated phosphoinositides (PIP(n) with 3-4 double bonds), T(eff) cells have unique PIP(n) marked by saturated fatty acyl chains (0-2 double bonds). PIP(n) are precursors for second messengers. Polyunsaturated phosphatidylinositol bisphosphate (PIP(2)) exclusively supported signaling immediately upon T cell antigen receptor activation. In late T(eff) cells, activity of phospholipase C-gamma1, the enzyme that cleaves PIP(2) into downstream mediators, waned, and saturated PIP(n) became essential for sustained signaling. Saturated PIP was more rapidly converted to PIP(2) with subsequent recruitment of phospholipase C-gamma1, and loss of saturated PIP(n) impaired T(eff) cell fitness and function, even in cells with abundant polyunsaturated PIP(n). Glucose was the substrate for de novo PIP(n) synthesis, and was rapidly utilized for saturated PIP(2) generation. Thus, separate PIP(n) pools with distinct acyl chain compositions and metabolic dependencies drive important signaling events to initiate and then sustain effector function during CD8+ T cell differentiation. |
