PMID- 24356888
OWN - NLM
STAT- MEDLINE
DCOM- 20140623
LR  - 20231213
IS  - 1521-4141 (Electronic)
IS  - 0014-2980 (Print)
IS  - 0014-2980 (Linking)
VI  - 44
IP  - 4
DP  - 2014 Apr
TI  - CD5 enhances Th17-cell differentiation by regulating IFN-gamma response and RORgammat 
      localization.
PG  - 1137-42
LID - 10.1002/eji.201343998 [doi]
AB  - Mechanisms that modulate the generation of Th17 cells are incompletely 
      understood. We report that the activation of casein kinase 2 (CK2) by CD5 is 
      essential for the efficient generation of Th17 cells in vitro and in vivo. In our 
      study, the CD5-CK2 signaling pathway enhanced TCR-induced activation of AKT and 
      promoted the differentiation of Th17 cells by two independent mechanisms: 
      inhibition of glycogen synthase kinase 3 (GSK3) and activation of mTOR. Genetic 
      ablation of the CD5-CK2 signaling pathway attenuated TCR-induced AKT activation 
      and consequently increased activity of GSK3 in Th17 cells. This resulted in 
      increased sensitivity of Th17 cells to IFN-gamma-mediated inhibition. In the absence 
      of CD5-CK2 signaling, we observed decreased activity of S6K and attenuated 
      nuclear translocation of RORgammat (ROR is retinoic acid receptor related orphan 
      receptor). These results reveal a novel and essential function of the CD5-CK2 
      signaling pathway and GSK3-IFN-gamma axis in regulating Th-cell differentiation and 
      provide a possible means to dampen Th17-type responses in autoimmune diseases.
CI  - (c) 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - McGuire, Donald J
AU  - McGuire DJ
AD  - Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, 
      USA.
FAU - Rowse, Amber L
AU  - Rowse AL
FAU - Li, Hao
AU  - Li H
FAU - Peng, Binghao J
AU  - Peng BJ
FAU - Sestero, Christine M
AU  - Sestero CM
FAU - Cashman, Kevin S
AU  - Cashman KS
FAU - De Sarno, Patrizia
AU  - De Sarno P
FAU - Raman, Chander
AU  - Raman C
LA  - eng
GR  - P30 AI027767/AI/NIAID NIH HHS/United States
GR  - T32 AI007051/AI/NIAID NIH HHS/United States
GR  - AI1076562/AI/NIAID NIH HHS/United States
GR  - T32 NS048039/NS/NINDS NIH HHS/United States
GR  - P30 AR048311/AR/NIAMS NIH HHS/United States
GR  - R01 AI076562/AI/NIAID NIH HHS/United States
GR  - T32-AI007051/AI/NIAID NIH HHS/United States
GR  - R01 NS064261/NS/NINDS NIH HHS/United States
GR  - G20 RR022807/RR/NCRR NIH HHS/United States
GR  - G20 RR025858/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140116
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (CD5 Antigens)
RN  - 0 (Cd5 protein, mouse)
RN  - 0 (Nuclear Receptor Subfamily 1, Group F, Member 3)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Receptors, Interferon)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.11.1 (Casein Kinase II)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Animals
MH  - CD5 Antigens/genetics/*immunology/metabolism
MH  - Casein Kinase II/genetics/immunology/metabolism
MH  - Cell Differentiation/drug effects/genetics/*immunology
MH  - Cell Nucleus/immunology/metabolism
MH  - Cells, Cultured
MH  - Flow Cytometry
MH  - Glycogen Synthase Kinase 3/immunology/metabolism
MH  - Immunohistochemistry
MH  - Interferon-gamma/*immunology/metabolism/pharmacology
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Nuclear Receptor Subfamily 1, Group F, Member 3/*immunology/metabolism
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/immunology/metabolism
MH  - Receptors, Antigen, T-Cell/genetics/immunology/metabolism
MH  - Receptors, Interferon/immunology/metabolism
MH  - Signal Transduction/genetics/immunology
MH  - Th17 Cells/*immunology/metabolism
MH  - Interferon gamma Receptor
PMC - PMC3984608
MID - NIHMS553953
OTO - NOTNLM
OT  - AKT
OT  - CD5
OT  - Cytokine receptor signaling
OT  - Glycogen synthase kinase 3
OT  - Th17
COIS- DISCLOSURES The authors have no financial conflicts of interest.
EDAT- 2013/12/21 06:00
MHDA- 2014/06/24 06:00
PMCR- 2015/04/01
CRDT- 2013/12/21 06:00
PHST- 2013/08/14 00:00 [received]
PHST- 2013/11/07 00:00 [revised]
PHST- 2013/12/13 00:00 [accepted]
PHST- 2013/12/21 06:00 [entrez]
PHST- 2013/12/21 06:00 [pubmed]
PHST- 2014/06/24 06:00 [medline]
PHST- 2015/04/01 00:00 [pmc-release]
AID - 10.1002/eji.201343998 [doi]
PST - ppublish
SO  - Eur J Immunol. 2014 Apr;44(4):1137-42. doi: 10.1002/eji.201343998. Epub 2014 Jan 
      16.