Abstract
IL-7 signalling is important in regulating both survival and cellular size (growth) of T cells. While glucose metabolism has previously been implicated in the mechanism of IL-7 induced survival and growth, the role of amino acids has not before been reported. Here, we show IL-7 dependent T cell survival does not require either exogenous glucose or amino acids. In contrast, maintenance of cell size and IL-7 induced growth were specifically dependent on amino acids. Furthermore, cellular amino acid uptake was implicated in the mechanism of IL-7 induced growth. Analysis of IL-7 regulated gene expression revealed that neutral and cationic amino acid transporters were specific transcriptional targets of IL-7 signalling. In contrast, none of the four glucose transporters expressed in T cells were modulated. Taken together, these data reveal for the first time the central importance of amino acid homeostasis for IL-7 regulated T cell growth.
Highlights
The cytokine IL-7 is essential for normal T cell homeostasis
Maintenance of a cell size comparable to that of ex vivo CD8 T cells required that IL-7 was at least 10 ng/ml, while growth resulting in increased cell size was observed at doses above 10 ng/ ml (Fig. 1B)
We found no evidence of transcriptional regulation of any of the glucose transporters expressed in F5 T cells
Summary
The cytokine IL-7 is essential for normal T cell homeostasis Both thymopoesis [1,2] and survival of peripheral naıve T cells [3,4,5] are dependent on IL-7 signalling. IL-7 induced growth in cellular size is sensitive to PI3kinase and mTOR inhibitors, suggesting that IL-7 signalling via a PI3kinase, Akt and mTOR dependent pathway is involved [12]. We compared the requirement for glucose and amino acids for IL-7 dependent survival and growth of T cells. While T cell survival in response to IL-7 stimulation occurred independently of either nutrients, IL-7 induced growth of cells was entirely dependent on the presence of amino acids in culture medium. Analysis of IL-7 regulated gene transcription revealed that amino acid transporter expression is a specific target of IL-7 signalling
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