PMID- 22019834
OWN - NLM
STAT- MEDLINE
DCOM- 20120709
LR  - 20211020
IS  - 1529-2916 (Electronic)
IS  - 1529-2908 (Print)
IS  - 1529-2908 (Linking)
VI  - 12
IP  - 12
DP  - 2011 Oct 23
TI  - Expression of A20 by dendritic cells preserves immune homeostasis and prevents 
      colitis and spondyloarthritis.
PG  - 1184-93
LID - 10.1038/ni.2135 [doi]
AB  - Dendritic cells (DCs), which are known to support immune activation during 
      infection, may also regulate immune homeostasis in resting animals. Here we show 
      that mice lacking the ubiquitin-editing molecule A20 specifically in DCs 
      spontaneously showed DC activation and population expansion of activated T cells. 
      Analysis of DC-specific epistasis in compound mice lacking both A20 and the 
      signaling adaptor MyD88 specifically in DCs showed that A20 restricted both 
      MyD88-independent signals, which drive activation of DCs and T cells, and 
      MyD88-dependent signals, which drive population expansion of T cells. In 
      addition, mice lacking A20 specifically in DCs spontaneously developed 
      lymphocyte-dependent colitis, seronegative ankylosing arthritis and enthesitis, 
      conditions stereotypical of human inflammatory bowel disease (IBD). Our findings 
      indicate that DCs need A20 to preserve immune quiescence and suggest that 
      A20-dependent DC functions may underlie IBD and IBD-associated arthritides.
FAU - Hammer, Gianna Elena
AU  - Hammer GE
AD  - Department of Medicine, University of California at San Francisco, San Francisco, 
      California, USA.
FAU - Turer, Emre E
AU  - Turer EE
FAU - Taylor, Kimberly E
AU  - Taylor KE
FAU - Fang, Celia J
AU  - Fang CJ
FAU - Advincula, Rommel
AU  - Advincula R
FAU - Oshima, Shigeru
AU  - Oshima S
FAU - Barrera, Julio
AU  - Barrera J
FAU - Huang, Eric J
AU  - Huang EJ
FAU - Hou, Baidong
AU  - Hou B
FAU - Malynn, Barbara A
AU  - Malynn BA
FAU - Reizis, Boris
AU  - Reizis B
FAU - DeFranco, Anthony
AU  - DeFranco A
FAU - Criswell, Lindsey A
AU  - Criswell LA
FAU - Nakamura, Mary C
AU  - Nakamura MC
FAU - Ma, Averil
AU  - Ma A
LA  - eng
GR  - R01 DK095693/DK/NIDDK NIH HHS/United States
GR  - R01 DK071939/DK/NIDDK NIH HHS/United States
GR  - 076113/WT_/Wellcome Trust/United Kingdom
GR  - T32 DK007007/DK/NIDDK NIH HHS/United States
GR  - 085475/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20111023
PL  - United States
TA  - Nat Immunol
JT  - Nature immunology
JID - 100941354
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Nuclear Proteins)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 3.4.19.12 (TNFAIP3 protein, human)
RN  - EC 3.4.19.12 (Tumor Necrosis Factor alpha-Induced Protein 3)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.22.- (Tnfaip3 protein, mouse)
SB  - IM
MH  - Animals
MH  - Colitis/*immunology/pathology/prevention & control
MH  - Crohn Disease/genetics
MH  - Cysteine Endopeptidases
MH  - DNA-Binding Proteins/*genetics/metabolism
MH  - Dendritic Cells/*immunology/metabolism
MH  - Genetic Predisposition to Disease
MH  - Homeostasis/immunology
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/*genetics/*metabolism
MH  - Lymphatic Diseases/genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Myeloid Differentiation Factor 88/metabolism
MH  - Nuclear Proteins/genetics
MH  - Polymorphism, Single Nucleotide
MH  - Signal Transduction
MH  - Splenomegaly/genetics
MH  - Spondylitis, Ankylosing/*immunology/pathology/prevention & control
MH  - T-Lymphocytes/immunology
MH  - Tumor Necrosis Factor alpha-Induced Protein 3
MH  - Ubiquitin-Protein Ligases/*genetics/metabolism
PMC - PMC3419270
MID - NIHMS323369
COIS- The authors declare no competing financial interests.
EDAT- 2011/10/25 06:00
MHDA- 2012/07/10 06:00
PMCR- 2012/08/14
CRDT- 2011/10/25 06:00
PHST- 2011/02/07 00:00 [received]
PHST- 2011/09/07 00:00 [accepted]
PHST- 2011/10/25 06:00 [entrez]
PHST- 2011/10/25 06:00 [pubmed]
PHST- 2012/07/10 06:00 [medline]
PHST- 2012/08/14 00:00 [pmc-release]
AID - ni.2135 [pii]
AID - 10.1038/ni.2135 [doi]
PST - epublish
SO  - Nat Immunol. 2011 Oct 23;12(12):1184-93. doi: 10.1038/ni.2135.