PMID- 22491252
OWN - NLM
STAT- MEDLINE
DCOM- 20120807
LR  - 20211021
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 188
IP  - 10
DP  - 2012 May 15
TI  - Usp18 promotes conventional CD11b+ dendritic cell development.
PG  - 4776-81
LID - 10.4049/jimmunol.1101609 [doi]
AB  - Dendritic cells (DCs) represent the key cells linking innate and adaptive immune 
      responses. It is critical to understand the molecular factors regulating DC 
      differentiation. Usp18 is an IFN-inducible member of the ubiquitin-specific 
      protease family, which deconjugates ubiquitin-like modifier ISG15 from target 
      proteins and competitively inhibits IFN-alpha/beta-induced JAK/STAT activation. This 
      study demonstrates that the frequency of conventional CD11b(+) DCs in the spleen 
      of Usp18(-/-) mice was significantly reduced, whereas the frequencies of 
      conventional CD8(+) DCs and plasmacytoid DCs remained normal. In addition, 
      Usp18(-/-) bone marrow (BM) cells generate DCs less efficiently in 
      GM-CSF-supplemented culture, demonstrating a fundamental defect throughout the DC 
      differentiation pathway. Usp18(-/-) BM cells were rescued by exogenous expression 
      of either wild-type or deconjugation-inactive Usp18, and superimposition of an 
      IFN-alpha/beta receptor knockout returned in vivo DC populations to normal, clearly 
      showing that the defect seen is due solely to Usp18's effect on IFN signaling. 
      Finally, Usp18(-/-) BM-derived DCs expressed high levels of SOCS1/SOCS3, known 
      inhibitors of GM-CSF signaling, providing a mechanistic explanation for the 
      phenotype. In conclusion, we have identified a novel role of Usp18 in modulating 
      conventional CD11b(+) DC development via its inhibitory effect on type I IFN 
      signaling.
FAU - Cong, Xiu-Li
AU  - Cong XL
AD  - Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, 
      USA.
FAU - Lo, Miao-Chia
AU  - Lo MC
FAU - Reuter, Brian A
AU  - Reuter BA
FAU - Yan, Ming
AU  - Yan M
FAU - Fan, Jun-Bao
AU  - Fan JB
FAU - Zhang, Dong-Er
AU  - Zhang DE
LA  - eng
GR  - R01 HL091549/HL/NHLBI NIH HHS/United States
GR  - R01 HL091549-14/HL/NHLBI NIH HHS/United States
GR  - HL091549/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120409
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (CD11b Antigen)
RN  - 0 (CD8 Antigens)
RN  - 0 (Growth Substances)
RN  - 0 (Socs1 protein, mouse)
RN  - 0 (Socs3 protein, mouse)
RN  - 0 (Suppressor of Cytokine Signaling 1 Protein)
RN  - 0 (Suppressor of Cytokine Signaling 3 Protein)
RN  - 0 (Suppressor of Cytokine Signaling Proteins)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - EC 3.4.- (Endopeptidases)
RN  - EC 3.4.19.- (Usp18 protein, mouse)
RN  - EC 3.4.19.12 (Ubiquitin Thiolesterase)
SB  - IM
MH  - Animals
MH  - CD11b Antigen/*biosynthesis
MH  - CD8 Antigens/biosynthesis
MH  - Cell Count
MH  - Cell Differentiation/genetics/*immunology
MH  - Cells, Cultured
MH  - Dendritic Cells/cytology/enzymology/*immunology
MH  - Down-Regulation/genetics/immunology
MH  - Endopeptidases/deficiency/genetics/*physiology
MH  - Female
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/antagonists & 
      inhibitors/physiology
MH  - Growth Substances/deficiency/genetics/physiology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Suppressor of Cytokine Signaling 1 Protein
MH  - Suppressor of Cytokine Signaling 3 Protein
MH  - Suppressor of Cytokine Signaling Proteins/biosynthesis/physiology
MH  - Ubiquitin Thiolesterase
PMC - PMC3345079
MID - NIHMS363172
COIS- Conflict-of-interest disclosure The authors declare no competing financial 
      interests
EDAT- 2012/04/12 06:00
MHDA- 2012/08/08 06:00
PMCR- 2013/05/15
CRDT- 2012/04/12 06:00
PHST- 2012/04/12 06:00 [entrez]
PHST- 2012/04/12 06:00 [pubmed]
PHST- 2012/08/08 06:00 [medline]
PHST- 2013/05/15 00:00 [pmc-release]
AID - jimmunol.1101609 [pii]
AID - 10.4049/jimmunol.1101609 [doi]
PST - ppublish
SO  - J Immunol. 2012 May 15;188(10):4776-81. doi: 10.4049/jimmunol.1101609. Epub 2012 
      Apr 9.