Howie 2014 Front Immunol
| Howie D, Waldmann H, Cobbold S (2014) Nutrient sensing via mTOR in T cells maintains a tolerogenic microenvironment. Front Immunol 5:409. https://doi.org/10.3389/fimmu.2014.00409 |
Howie D, Waldmann H, Cobbold S (2014) Front Immunol
Abstract: We have proposed that tolerance can be maintained through the induction, by Treg cells, of a tolerogenic microenvironment within tolerated tissues that inhibits effector cell activity but which supports the generation of further Treg cells by "infectious tolerance." Two important components of this tolerogenic microenvironment depend on metabolism and nutrient sensing. The first is due to the up-regulation of multiple enzymes that consume essential amino acids, which are sensed in naΓ―ve T cells primarily via inhibition of the mechanistic target of rapamycin (mTOR) pathway, which in turn encourages their further differentiation into FOXP3(+) Treg cells. The second mechanism is the metabolism of extracellular ATP to adenosine by the ectoenzymes CD39 and CD73. These two enzymes are constitutively co-expressed on Treg cells, but can also be induced on a wide variety of cell types by TGFΞ² and the adenosine generated can be shown to be a potent inhibitor of T cell proliferation. This review will focus on mechanisms of nutrient sensing in T cells, how these are integrated with TCR and cytokine signals via the mTOR pathway, and what impact this has on intracellular metabolism and subsequently the control of differentiation into different effector or regulatory T cell subsets.
β’ Bioblast editor: Gnaiger E
Correction: FADH2 and Complex II
- FADH2 is shown as the substrate feeding electrons into Complex II (CII). This is wrong and requires correction - for details see Gnaiger (2024).
- Gnaiger E (2024) Complex II ambiguities β FADH2 in the electron transfer system. J Biol Chem 300:105470. https://doi.org/10.1016/j.jbc.2023.105470 - Β»Bioblast linkΒ«
