PMID- 21145759
OWN - NLM
STAT- MEDLINE
DCOM- 20110509
LR  - 20211203
IS  - 1097-4180 (Electronic)
IS  - 1074-7613 (Print)
IS  - 1074-7613 (Linking)
VI  - 33
IP  - 6
DP  - 2010 Dec 14
TI  - An oscillatory switch in mTOR kinase activity sets regulatory T cell 
      responsiveness.
PG  - 929-41
LID - 10.1016/j.immuni.2010.11.024 [doi]
AB  - There is a discrepancy between the in vitro anergic state of 
      CD4(+)CD25(hi)FoxP3(+) regulatory T (Treg) cells and their in vivo proliferative 
      capability. The underlying mechanism of this paradox is unknown. Here we show 
      that the anergic state of Treg cells depends on the elevated activity of the 
      mammalian target of rapamycin (mTOR) pathway induced by leptin: a transient 
      inhibition of mTOR with rapamycin, before T cell receptor (TCR) stimulation, made 
      Treg cells highly proliferative in the absence of exogenous interleukin-2 (IL-2). 
      This was a dynamic and oscillatory phenomenon characterized by an early 
      downregulation of the leptin-mTOR pathway followed by an increase in mTOR 
      activation necessary for Treg cell expansion to occur. These data suggest that 
      energy metabolism, through the leptin-mTOR-axis, sets responsiveness of Treg 
      cells that use this information to control immune tolerance and autoimmunity.
FAU - Procaccini, Claudio
AU  - Procaccini C
AD  - Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, 
      Consiglio Nazionale delle Ricerche (IEOS-CNR), Napoli 80131, Italy.
FAU - De Rosa, Veronica
AU  - De Rosa V
FAU - Galgani, Mario
AU  - Galgani M
FAU - Abanni, Luisa
AU  - Abanni L
FAU - Cali, Gaetano
AU  - Cali G
FAU - Porcellini, Antonio
AU  - Porcellini A
FAU - Carbone, Fortunata
AU  - Carbone F
FAU - Fontana, Silvia
AU  - Fontana S
FAU - Horvath, Tamas L
AU  - Horvath TL
FAU - La Cava, Antonio
AU  - La Cava A
FAU - Matarese, Giuseppe
AU  - Matarese G
LA  - eng
GR  - DP1 OD006850/OD/NIH HHS/United States
GR  - DO10D006850/PHS HHS/United States
GR  - 202579/ERC_/European Research Council/International
GR  - AR53239/AR/NIAMS NIH HHS/United States
GR  - R01 AR053239-05/AR/NIAMS NIH HHS/United States
GR  - GJT08004/TI_/Telethon/Italy
GR  - R01 AR053239/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20101209
PL  - United States
TA  - Immunity
JT  - Immunity
JID - 9432918
RN  - 0 (CD4 Antigens)
RN  - 0 (FOXP3 protein, human)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Interleukin-2)
RN  - 0 (Interleukin-2 Receptor alpha Subunit)
RN  - 0 (Leptin)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
CIN - Nat Rev Immunol. 2011 Feb;11(2):72. PMID: 21467973
MH  - Animals
MH  - CD4 Antigens/biosynthesis
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Clonal Anergy/drug effects/genetics
MH  - Disease Progression
MH  - Encephalomyelitis, Autoimmune, Experimental/drug 
      therapy/immunology/*metabolism/physiopathology
MH  - Forkhead Transcription Factors/biosynthesis
MH  - Humans
MH  - Interleukin-2/immunology/metabolism
MH  - Interleukin-2 Receptor alpha Subunit/biosynthesis
MH  - Leptin/immunology/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Signal Transduction
MH  - Sirolimus/pharmacology/therapeutic use
MH  - T-Lymphocytes, Regulatory/drug effects/immunology/*metabolism/pathology
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/immunology/*metabolism
PMC - PMC3133602
MID - NIHMS306331
EDAT- 2010/12/15 06:00
MHDA- 2011/05/10 06:00
PMCR- 2011/12/14
CRDT- 2010/12/15 06:00
PHST- 2010/03/01 00:00 [received]
PHST- 2010/07/13 00:00 [revised]
PHST- 2010/10/22 00:00 [accepted]
PHST- 2010/12/15 06:00 [entrez]
PHST- 2010/12/15 06:00 [pubmed]
PHST- 2011/05/10 06:00 [medline]
PHST- 2011/12/14 00:00 [pmc-release]
AID - S1074-7613(10)00454-1 [pii]
AID - 10.1016/j.immuni.2010.11.024 [doi]
PST - ppublish
SO  - Immunity. 2010 Dec 14;33(6):929-41. doi: 10.1016/j.immuni.2010.11.024. Epub 2010 
      Dec 9.