IL-7-Induced Glycerol Transport and TAG Synthesis Promotes Memory CD8⁺ T Cell Longevity

 Cui G.L., et al. (2015) Cell 161, 750-761

Speaker: Chih-Yu Huang (黃智裕)                               Time: 15:10-16:00, Oct. 7, 2015

Commentator: Dr. Chi-Chang Hsieh (謝奇璋)            Place: Room 601

Abstract

    The longevity of memory T cells is critical for long-term immunity against reinfection ^[1], and is dependent on IL-7, which promotes T cell survival and self-renewal ^[2]. Additionally, recent studies have shown that after viral clearance, effector T cells that were once performing high rates of glycolysis and anabolic metabolism rest down and become more reliant on fatty acid oxidation and mitochondrial oxidative phosphorylation to generate energy ^[3]. The mechanism regarding how IL-7 mediates memory T cell survival, especially from the aspect of metabolic alteration, still remains elusive. Here, the authors identified that IL-7 induces the expression of aquaporin 9 (AQP9), a channel for glycerol transport, in memory CD8 T cells instead of naïve and effector T cells, and that AQP9 deficiency impairs memory CD8 T cell survival. AQP9 deficiency not only hinders glycerol import for triglyceride (TAG) synthesis and storage but also reduces ATP levels in memory CD8 T cells. Next, they showed that the impairment of AQP9-deficient memory CD8 T cell survival can be rescued by overexpression of TAG synthases, which increases the amount of lipid stores. IL-7 is able to directly enhance TAG synthesis to promote memory CD8 T cell survival. The IL-7-mediated TAG synthesis is vital for promoting memory CD8 T cell survival in both human cells and mice. In conclusion, they discover the underlying mechanism of how IL-7 mediates TAG synthesis to promote memory T cell longevity.

References

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2.     Kondrack R.M., et al. (2003) Interleukin 7 regulates the survival and generation of memory CD4 T cells. J. Exp. Med. 198, 1797-1806

3.     Fox C.J., et al. (2005) Fuel feeds function: energy metabolism and the T-cell response. Nat. Rev. Immunol. 5, 844-852