PMID- 22461492
OWN - NLM
STAT- MEDLINE
DCOM- 20120807
LR  - 20211021
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 119
IP  - 21
DP  - 2012 May 24
TI  - The tumor suppressor p15Ink4b regulates the differentiation and maturation of 
      conventional dendritic cells.
PG  - 5005-15
LID - 10.1182/blood-2011-10-387613 [doi]
AB  - The tumor suppressor p15Ink4b is frequently inactivated by methylation in acute 
      myeloid leukemia and premalignant myeloid disorders. Dendritic cells (DCs) as 
      potent APCs play critical regulatory roles in antileukemic immune responses. In 
      the present study, we investigated whether p15Ink4b can function as modulator of 
      DC development. The expression of p15Ink4b is induced strongly during 
      differentiation and activation of DCs, and its loss resulted in significant 
      quantitative and qualitative impairments of conventional DC (cDC) development. 
      Accordingly, ex vivo-generated BM-derived DCs from p15Ink4b-knockout mice express 
      significantly decreased levels of the antigen-presenting (MHC II) and 
      costimulatory (CD80 and CD86) molecules and have impaired immunostimulatory 
      functions, such as antigen uptake and T-cell stimulation. Reexpression of 
      p15Ink4b in progenitors restored these defects, and confirmed a positive role for 
      p15Ink4b during cDC differentiation and maturation. Furthermore, we have shown 
      herein that p15Ink4b expression increases phosphorylation of Erk1/Erk2 kinases, 
      which leads to an elevated activity of the PU.1 transcription factor. In 
      conclusion, our results establish p15Ink4b as an important modulator of cDC 
      development and implicate a novel function for this tumor suppressor in the 
      regulation of adaptive immune responses.
FAU - Fares, Joanna
AU  - Fares J
AD  - Laboratory of Cellular Oncology, National Cancer Institute, National Institutes 
      of Health, Bethesda, MD 20892, USA.
FAU - Koller, Richard
AU  - Koller R
FAU - Humeniuk, Rita
AU  - Humeniuk R
FAU - Wolff, Linda
AU  - Wolff L
FAU - Bies, Juraj
AU  - Bies J
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20120328
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p15)
RN  - 0 (Tumor Suppressor Proteins)
SB  - IM
MH  - Adaptive Immunity/genetics
MH  - Animals
MH  - Bone Marrow Cells/metabolism/physiology
MH  - Cell Differentiation/*genetics
MH  - Cells, Cultured
MH  - Cyclin-Dependent Kinase Inhibitor p15/genetics/metabolism/*physiology
MH  - DNA Methylation/physiology
MH  - Dendritic Cells/metabolism/*physiology
MH  - Gene Deletion
MH  - Gene Expression Regulation/immunology/physiology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Promoter Regions, Genetic/physiology
MH  - Tumor Suppressor Proteins/genetics/metabolism/physiology
PMC - PMC3367901
EDAT- 2012/03/31 06:00
MHDA- 2012/08/08 06:00
PMCR- 2013/05/24
CRDT- 2012/03/31 06:00
PHST- 2012/03/31 06:00 [entrez]
PHST- 2012/03/31 06:00 [pubmed]
PHST- 2012/08/08 06:00 [medline]
PHST- 2013/05/24 00:00 [pmc-release]
AID - S0006-4971(20)47822-X [pii]
AID - 2011/387613 [pii]
AID - 10.1182/blood-2011-10-387613 [doi]
PST - ppublish
SO  - Blood. 2012 May 24;119(21):5005-15. doi: 10.1182/blood-2011-10-387613. Epub 2012 
      Mar 28.