PMID- 21849678
OWN - NLM
STAT- MEDLINE
DCOM- 20111109
LR  - 20211020
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 187
IP  - 6
DP  - 2011 Sep 15
TI  - Ubiquitination of CD86 is a key mechanism in regulating antigen presentation by 
      dendritic cells.
PG  - 2966-73
LID - 10.4049/jimmunol.1101643 [doi]
AB  - Dendritic cells (DCs) require costimulatory molecules such as CD86 to efficiently 
      activate T cells for the induction of adaptive immunity. DCs maintain minimal 
      levels of CD86 expression at rest, but upregulate levels upon LPS stimulation. 
      LPS-stimulated DCs produce the immune suppressive cytokine IL-10 that acts in an 
      autocrine manner to regulate CD86 levels. Interestingly, the underlying molecular 
      mechanism behind the tight control of CD86 is not completely understood. In this 
      study, we report that CD86 is ubiquitinated in DCs via MARCH1 E3 ubiquitin ligase 
      and that this ubiquitination plays a key role in CD86 regulation. Ubiquitination 
      at lysine 267 played the most critical role for this regulation. CD86 is 
      ubiquitinated in MARCH1-deficient DCs to a much lesser degree than in wild-type 
      DCs, which also correlated with a significant increase in CD86 expression. 
      Importantly, CD86 is continuously ubiquitinated in DCs following activation by 
      LPS, and this was due to the autocrine IL-10 inhibition of MARCH1 downregulation. 
      Accordingly, DCs lacking MARCH1 and DCs expressing ubiquitination-resistant 
      mutant CD86 both failed to regulate CD86 in response to autocrine IL-10. DCs 
      expressing ubiquitination-resistant mutant CD86 failed to control their T 
      cell-activating abilities at rest as well as in response to autocrine IL-10. 
      These studies suggest that ubiquitination serves as an important mechanism by 
      which DCs control CD86 expression and regulate their Ag-presenting functions.
FAU - Baravalle, Gunther
AU  - Baravalle G
AD  - Department of Microbiology and Immunology, Sandler Asthma Basic Research Center, 
      University of California, San Francisco, San Francisco, CA 94143, USA.
FAU - Park, Hyesuk
AU  - Park H
FAU - McSweeney, Megan
AU  - McSweeney M
FAU - Ohmura-Hoshino, Mari
AU  - Ohmura-Hoshino M
FAU - Matsuki, Yohei
AU  - Matsuki Y
FAU - Ishido, Satoshi
AU  - Ishido S
FAU - Shin, Jeoung-Sook
AU  - Shin JS
LA  - eng
GR  - T32 AI007334/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110817
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (B7-2 Antigen)
RN  - 0 (Cd86 protein, mouse)
RN  - EC 2.3.2.27 (MARCH1 protein, mouse)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
MH  - Animals
MH  - Antigen Presentation/*immunology
MH  - B7-2 Antigen/immunology/*metabolism
MH  - Blotting, Western
MH  - Cell Separation
MH  - Dendritic Cells/*immunology/metabolism
MH  - Flow Cytometry
MH  - Gene Expression
MH  - Gene Expression Regulation/*immunology
MH  - Immunoprecipitation
MH  - Lymphocyte Activation/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - T-Lymphocytes/immunology
MH  - Ubiquitin-Protein Ligases/immunology/metabolism
MH  - Ubiquitination/*immunology
PMC - PMC4496154
MID - NIHMS703026
COIS- Disclosures The authors have no financial conflicts of interest.
EDAT- 2011/08/19 06:00
MHDA- 2011/11/10 06:00
PMCR- 2015/07/08
CRDT- 2011/08/19 06:00
PHST- 2011/08/19 06:00 [entrez]
PHST- 2011/08/19 06:00 [pubmed]
PHST- 2011/11/10 06:00 [medline]
PHST- 2015/07/08 00:00 [pmc-release]
AID - jimmunol.1101643 [pii]
AID - 10.4049/jimmunol.1101643 [doi]
PST - ppublish
SO  - J Immunol. 2011 Sep 15;187(6):2966-73. doi: 10.4049/jimmunol.1101643. Epub 2011 
      Aug 17.