PMID- 32839235
OWN - NLM
STAT- MEDLINE
DCOM- 20210329
LR  - 20211204
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 205
IP  - 7
DP  - 2020 Oct 1
TI  - Regulatory T Cell Stability and Migration Are Dependent on mTOR.
PG  - 1799-1809
LID - 10.4049/jimmunol.1901480 [doi]
AB  - CD4(+) Foxp3(+) regulatory T cells (Treg) are essential to maintain immune 
      tolerance, as their loss leads to a fatal autoimmune syndrome in mice and humans. 
      Conflicting findings have been reported concerning their metabolism. Some reports 
      found that Treg have low mechanistic target of rapamycin (mTOR) activity and 
      would be less dependent on this kinase compared with conventional T cells, 
      whereas other reports suggest quite the opposite. In this study, we revisited 
      this question by using mice that have a specific deletion of mTOR in Treg. These 
      mice spontaneously develop a severe and systemic inflammation. We show that mTOR 
      expression by Treg is critical for their differentiation into effector Treg and 
      their migration into nonlymphoid tissues. We also reveal that mTOR-deficient Treg 
      have reduced stability. This loss of Foxp3 expression is associated with partial 
      Foxp3 DNA remethylation, which may be due to an increased activity of the 
      glutaminolysis pathway. Thus, our work shows that mTOR is crucial for Treg 
      differentiation, migration, and identity and that drugs targeting this metabolism 
      pathway will impact on their biology.
CI  - Copyright (c) 2020 by The American Association of Immunologists, Inc.
FAU - Vallion, Romain
AU  - Vallion R
AD  - Centre d'Immunologie et des Maladies Infectieuses, Sorbonne Universite, INSERM, 
      CNRS, 75013 Paris, France.
FAU - Divoux, Jordane
AU  - Divoux J
AD  - Centre d'Immunologie et des Maladies Infectieuses, Sorbonne Universite, INSERM, 
      CNRS, 75013 Paris, France.
FAU - Glauzy, Salome
AU  - Glauzy S
AD  - Centre d'Immunologie et des Maladies Infectieuses, Sorbonne Universite, INSERM, 
      CNRS, 75013 Paris, France.
FAU - Ronin, Emilie
AU  - Ronin E
AUID- ORCID: 0000-0003-0295-7933
AD  - Centre d'Immunologie et des Maladies Infectieuses, Sorbonne Universite, INSERM, 
      CNRS, 75013 Paris, France.
FAU - Lombardi, Yannis
AU  - Lombardi Y
AD  - Centre d'Immunologie et des Maladies Infectieuses, Sorbonne Universite, INSERM, 
      CNRS, 75013 Paris, France.
FAU - Lubrano di Ricco, Martina
AU  - Lubrano di Ricco M
AD  - Centre d'Immunologie et des Maladies Infectieuses, Sorbonne Universite, INSERM, 
      CNRS, 75013 Paris, France.
FAU - Gregoire, Sylvie
AU  - Gregoire S
AD  - Centre d'Immunologie et des Maladies Infectieuses, Sorbonne Universite, INSERM, 
      CNRS, 75013 Paris, France.
FAU - Nemazanyy, Ivan
AU  - Nemazanyy I
AD  - Plateforme Etude du Metabolisme, Structure Federative de Recherche Necker, INSERM 
      US24/CNRS UMS 3633, Paris, France.
FAU - Durand, Aurelie
AU  - Durand A
AD  - Paris Descartes Universite, Sorbonne Paris Cite, Institut Cochin, CNRS UMR8104, 
      INSERM U1016, 75014 Paris, France; and.
FAU - Fradin, Delphine
AU  - Fradin D
AUID- ORCID: 0000-0001-6231-2649
AD  - CRCINA, Institut de Recherche en Sante de l'Universite de Nantes, 44007 Nantes, 
      France.
FAU - Lucas, Bruno
AU  - Lucas B
AUID- ORCID: 0000-0002-0322-3977
AD  - Paris Descartes Universite, Sorbonne Paris Cite, Institut Cochin, CNRS UMR8104, 
      INSERM U1016, 75014 Paris, France; and.
FAU - Salomon, Benoit L
AU  - Salomon BL
AD  - Centre d'Immunologie et des Maladies Infectieuses, Sorbonne Universite, INSERM, 
      CNRS, 75013 Paris, France; benoit.salomon@inserm.fr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200824
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Foxp3 protein, mouse)
RN  - 0RH81L854J (Glutamine)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Autoimmunity/genetics
MH  - Cell Differentiation
MH  - Cell Movement
MH  - DNA Methylation
MH  - Forkhead Transcription Factors/genetics/*metabolism
MH  - Glutamine/metabolism
MH  - Inflammation/*genetics
MH  - Lymphocyte Activation
MH  - Mice
MH  - Mice, Knockout
MH  - Mutation/genetics
MH  - Signal Transduction
MH  - T-Lymphocytes, Regulatory/*immunology
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
EDAT- 2020/08/26 06:00
MHDA- 2021/03/30 06:00
CRDT- 2020/08/26 06:00
PHST- 2019/12/16 00:00 [received]
PHST- 2020/07/24 00:00 [accepted]
PHST- 2020/08/26 06:00 [pubmed]
PHST- 2021/03/30 06:00 [medline]
PHST- 2020/08/26 06:00 [entrez]
AID - jimmunol.1901480 [pii]
AID - 10.4049/jimmunol.1901480 [doi]
PST - ppublish
SO  - J Immunol. 2020 Oct 1;205(7):1799-1809. doi: 10.4049/jimmunol.1901480. Epub 2020 
      Aug 24.