PMID- 22031758
OWN - NLM
STAT- MEDLINE
DCOM- 20120113
LR  - 20211020
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 187
IP  - 11
DP  - 2011 Dec 1
TI  - Immune regulation through mitochondrion-dependent dendritic cell death induced by 
      T regulatory cells.
PG  - 5684-92
LID - 10.4049/jimmunol.1101834 [doi]
AB  - Dendritic cells (DCs) harbor an active mitochondrion-dependent cell death pathway 
      regulated by Bcl-2 family members and undergo rapid turnover in vivo. However, 
      the functions for mitochondrion-dependent cell death of DCs in immune regulation 
      remain to be elucidated. In this article, we show that DC-specific knockout of 
      proapoptotic Bcl-2 family members, Bax and Bak, induced spontaneous T cell 
      activation and autoimmunity in mice. In addition to a defect in spontaneous cell 
      death, Bax(-/-)Bak(-/-) DCs were resistant to killing by CD4(+)Foxp3(+) T 
      regulatory cells (Tregs) compared with wild-type DCs. Tregs inhibited the 
      activation of T effector cells by wild-type, but not Bax(-/-)Bak(-/-), DCs. 
      Bax(-/-)Bak(-/-) DCs showed increased propensity for inducing autoantibodies. 
      Moreover, the autoimmune potential of Bax(-/-)Bak(-/-) DCs was resistant to 
      suppression by Tregs. Our data suggested that Bax and Bak mediate intrinsic 
      spontaneous cell death in DCs, as well as regulate DC killing triggered by Tregs. 
      Bax- and Bak-dependent cell death mechanisms help to maintain DC homeostasis and 
      contribute to the regulation of T cell activation and the suppression of 
      autoimmunity.
FAU - Chen, Min
AU  - Chen M
AD  - Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 
      77030, USA.
FAU - Felix, Kumar
AU  - Felix K
FAU - Wang, Jin
AU  - Wang J
LA  - eng
GR  - R01 AI074949-01/AI/NIAID NIH HHS/United States
GR  - R01 AI074949-05/AI/NIAID NIH HHS/United States
GR  - R01 DK083164-01/DK/NIDDK NIH HHS/United States
GR  - R01 AI074949-04/AI/NIAID NIH HHS/United States
GR  - R01 GM087710/GM/NIGMS NIH HHS/United States
GR  - R01 AI074949-03/AI/NIAID NIH HHS/United States
GR  - R01 DK083164-04/DK/NIDDK NIH HHS/United States
GR  - R01 DK083164-03/DK/NIDDK NIH HHS/United States
GR  - R01 GM087710-09/GM/NIGMS NIH HHS/United States
GR  - R01DK083164/DK/NIDDK NIH HHS/United States
GR  - R01 DK083164-02/DK/NIDDK NIH HHS/United States
GR  - R01 AI074949-02/AI/NIAID NIH HHS/United States
GR  - R01 GM087710-06A2/GM/NIGMS NIH HHS/United States
GR  - R01 GM087710-08/GM/NIGMS NIH HHS/United States
GR  - R01 GM087710-07/GM/NIGMS NIH HHS/United States
GR  - R01AI074949/AI/NIAID NIH HHS/United States
GR  - R01 AI074949/AI/NIAID NIH HHS/United States
GR  - R01 DK083164/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20111026
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (bcl-2 Homologous Antagonist-Killer Protein)
RN  - 0 (bcl-2-Associated X Protein)
SB  - IM
MH  - Adoptive Transfer
MH  - Animals
MH  - Apoptosis/*immunology
MH  - Autoimmunity/*immunology
MH  - Cell Separation
MH  - Dendritic Cells/*immunology/metabolism
MH  - Flow Cytometry
MH  - Immunohistochemistry
MH  - Lymphocyte Activation/immunology
MH  - Mice
MH  - Mice, Knockout
MH  - Self Tolerance/*immunology
MH  - T-Lymphocytes, Regulatory/*immunology/metabolism
MH  - bcl-2 Homologous Antagonist-Killer Protein/immunology/metabolism
MH  - bcl-2-Associated X Protein/immunology/metabolism
PMC - PMC3282618
MID - NIHMS328138
EDAT- 2011/10/28 06:00
MHDA- 2012/01/14 06:00
PMCR- 2012/12/01
CRDT- 2011/10/28 06:00
PHST- 2011/10/28 06:00 [entrez]
PHST- 2011/10/28 06:00 [pubmed]
PHST- 2012/01/14 06:00 [medline]
PHST- 2012/12/01 00:00 [pmc-release]
AID - jimmunol.1101834 [pii]
AID - 10.4049/jimmunol.1101834 [doi]
PST - ppublish
SO  - J Immunol. 2011 Dec 1;187(11):5684-92. doi: 10.4049/jimmunol.1101834. Epub 2011 
      Oct 26.