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Comment
. 2018 Jul;15(7):657-659.
doi: 10.1038/cmi.2017.110. Epub 2017 Oct 30.

S1P: the elixir of life for naive T cells

Michaël Pérès  1   2   3   4 , Anne Montfort  1   4 , Nathalie Andrieu-Abadie  1   4 , Céline Colacios  1   2   4 , Bruno Ségui  5   6   7
Affiliations
Comment

S1P: the elixir of life for naive T cells

Michaël Pérès et al. Cell Mol Immunol. 2018 Jul.
No abstract available

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
S1P from lymphatic endothelial cells (LEC) is secreted in a SPNS2-dependent manner, promoting naive T-cell survival via S1P1. Sphingosine kinases (SK) 1/2 transform sphingosine into S1P, which is secreted by LEC through the specific transporter SPNS2. S1P can be dephosphorylated by S1P phosphatases 1/2 (SPPases) or irreversibly degraded into phosphoethanolamine (PE) and hexadecenal by S1P lyase (SPL). Inhibition of SPL by DOP (deoxypyridoxine) increases the level of S1P in lymph nodes. S1P binds to S1P1 expressed by naive T cells, which then survive most likely upon activation of the AKT pathway. SPNS2 or S1P1 deficiency impairs this signaling, inducing loss of mitochondria and subsequent apoptosis. Mechanistically, PINK1 accumulates in mitochondria and induces ubiquitinylation of mitochondrial proteins, leading to mitophagy. Overexpression of Bcl-2 counteracts apoptosis induced by the loss of S1P/S1P1 signaling. Bcl-2, B cell lymphoma 2; PINK1, PTEN-induced putative kinase 1; S1P, sphingosine-1-phosphate; S1P1, S1P receptor 1; Ubq, Ubiquitin.
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