PMID- 27613697
OWN - NLM
STAT- MEDLINE
DCOM- 20170814
LR  - 20211204
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 197
IP  - 8
DP  - 2016 Oct 15
TI  - Context-Specific Function of S6K2 in Th Cell Differentiation.
PG  - 3049-3058
AB  - The mammalian target of rapamycin (mTOR) is essential for Th cell proliferation 
      and effector differentiation, making the mTOR signaling network an attractive 
      immunomodulatory target for autoimmune-related diseases. Although direct 
      targeting of mTOR complex-1 (mTORC1) with rapamycin can provide clinical benefit, 
      targeting downstream enzymes has the potential to offer more selective 
      immunosuppression. In this study, we evaluated p70 ribosomal protein S6 Kinase 2 
      (S6K2), a downstream effector of mTORC1, for its role in T cell function and 
      autoimmunity. S6K2 is a direct substrate of mTORC1, with a potential role in Th17 
      differentiation suggested by biochemical studies. Using a genetic approach with 
      S6K2 knockout mice, we found that S6K2 loss reduces Th17 skewing and increases 
      regulatory T cell differentiation in vitro when cultured in RPMI 1640 media. 
      However, S6K2 was dispensable for Th17 differentiation in IMDM. In an in vivo 
      experimental autoimmune encephalomyelitis model in which rapamycin suppresses 
      disease, S6K2 knockout mice did not exhibit differences in clinical score or Th17 
      differentiation. These results suggest that S6K2 is dispensable for Th17-driven 
      autoimmunity and highlight how distinct experimental conditions can produce 
      significantly different results in T cell differentiation.
CI  - Copyright (c) 2016 by The American Association of Immunologists, Inc.
FAU - Pai, Christine
AU  - Pai C
AUID- ORCID: 0000-0002-4369-4001
AD  - Department of Molecular Biology and Biochemistry, Institute for Immunology, 
      University of California, Irvine, Irvine, CA 92697.
FAU - Walsh, Craig M
AU  - Walsh CM
AD  - Department of Molecular Biology and Biochemistry, Institute for Immunology, 
      University of California, Irvine, Irvine, CA 92697.
FAU - Fruman, David A
AU  - Fruman DA
AUID- ORCID: 0000-0002-1796-5162
AD  - Department of Molecular Biology and Biochemistry, Institute for Immunology, 
      University of California, Irvine, Irvine, CA 92697 dfruman@uci.edu.
LA  - eng
GR  - P30 CA062203/CA/NCI NIH HHS/United States
GR  - R21 AI099656/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20160909
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Immunologic Factors)
RN  - 0 (Multiprotein Complexes)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Autoimmune Diseases/immunology/*therapy
MH  - Autoimmunity
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Immunologic Factors/*therapeutic use
MH  - Immunosuppression Therapy
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Multiprotein Complexes/*metabolism
MH  - Ribosomal Protein S6 Kinases, 70-kDa/genetics/*metabolism
MH  - Sirolimus/therapeutic use
MH  - Substrate Specificity
MH  - T-Lymphocytes, Regulatory/*immunology
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Th17 Cells/*immunology
PMC - PMC5101169
MID - NIHMS810856
EDAT- 2016/09/11 06:00
MHDA- 2017/08/15 06:00
PMCR- 2017/10/15
CRDT- 2016/09/11 06:00
PHST- 2016/01/27 00:00 [received]
PHST- 2016/08/11 00:00 [accepted]
PHST- 2016/09/11 06:00 [pubmed]
PHST- 2017/08/15 06:00 [medline]
PHST- 2016/09/11 06:00 [entrez]
PHST- 2017/10/15 00:00 [pmc-release]
AID - jimmunol.1600167 [pii]
AID - 10.4049/jimmunol.1600167 [doi]
PST - ppublish
SO  - J Immunol. 2016 Oct 15;197(8):3049-3058. doi: 10.4049/jimmunol.1600167. Epub 2016 
      Sep 9.