PMID- 25221554
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140915
LR  - 20211021
IS  - 1664-3224 (Print)
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 5
DP  - 2014
TI  - Nutrient Sensing via mTOR in T Cells Maintains a Tolerogenic Microenvironment.
PG  - 409
LID - 10.3389/fimmu.2014.00409 [doi]
LID - 409
AB  - 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 naive 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 TGFbeta 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.
FAU - Howie, Duncan
AU  - Howie D
AD  - Sir William Dunn School of Pathology, University of Oxford , Oxford , UK.
FAU - Waldmann, Herman
AU  - Waldmann H
AD  - Sir William Dunn School of Pathology, University of Oxford , Oxford , UK.
FAU - Cobbold, Stephen
AU  - Cobbold S
AD  - Sir William Dunn School of Pathology, University of Oxford , Oxford , UK.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20140828
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
PMC - PMC4147234
OTO - NOTNLM
OT  - T cell differentiation
OT  - immune regulation
OT  - mTOR
OT  - metabolism
OT  - tolerance
EDAT- 2014/09/16 06:00
MHDA- 2014/09/16 06:01
PMCR- 2014/01/01
CRDT- 2014/09/16 06:00
PHST- 2014/07/01 00:00 [received]
PHST- 2014/08/13 00:00 [accepted]
PHST- 2014/09/16 06:00 [entrez]
PHST- 2014/09/16 06:00 [pubmed]
PHST- 2014/09/16 06:01 [medline]
PHST- 2014/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2014.00409 [doi]
PST - epublish
SO  - Front Immunol. 2014 Aug 28;5:409. doi: 10.3389/fimmu.2014.00409. eCollection 
      2014.