PMID- 21918189
OWN - NLM
STAT- MEDLINE
DCOM- 20111115
LR  - 20161125
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 187
IP  - 8
DP  - 2011 Oct 15
TI  - Wnt5a skews dendritic cell differentiation to an unconventional phenotype with 
      tolerogenic features.
PG  - 4129-39
LID - 10.4049/jimmunol.1101243 [doi]
AB  - Dendritic cells (DCs) are critical regulators of immune responses that integrate 
      signals from the innate and adaptive immune system and orchestrate T cell 
      responses toward either immunity or tolerance. Growing evidence points to the Wnt 
      signaling pathway as a pivotal piece in the immune balance and focuses on DCs as 
      a direct target for their immunoregulatory role. Our results show that the 
      increase in Wnt5a signaling during the differentiation of human DCs from 
      monocytes alters their phenotype and compromises their subsequent capacity to 
      mature in response to TLR-dependent stimuli. These Wnt5a-DCs produce scant 
      amounts of IL-12p70 and TNF-alpha but increased levels of IL-10. Consequently, these 
      Wnt5a-DCs have a reduced capacity to induce Th1 responses that promote IL-10 
      secretion by CD4 T cells. Changes in the transcriptional profile of Wnt5a-DCs 
      correlate with their unconventional phenotype caused presumably by increased 
      IL-6/IL-10 signaling during the process of DC differentiation. The effect of 
      Wnt5a is not a consequence of beta-catenin accumulation but is dependent on 
      noncanonical Ca(2+)/calmodulin-dependent protein kinase II/NF-kappaB signaling. Our 
      results therefore suggest that under high levels of Wnt5a, typical of the 
      inflammatory state and sepsis, monocytes could differentiate into unconventional 
      DCs with tolerogenic features.
FAU - Valencia, Jaris
AU  - Valencia J
AD  - Department of Cell Biology, Faculty of Medicine, Complutense University, 28040 
      Madrid, Spain.
FAU - Hernandez-Lopez, Carmen
AU  - Hernandez-Lopez C
FAU - Martinez, Victor G
AU  - Martinez VG
FAU - Hidalgo, Laura
AU  - Hidalgo L
FAU - Zapata, Agustin G
AU  - Zapata AG
FAU - Vicente, Angeles
AU  - Vicente A
FAU - Varas, Alberto
AU  - Varas A
FAU - Sacedon, Rosa
AU  - Sacedon R
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110914
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (WNT5A protein, human)
RN  - 0 (Wnt Proteins)
RN  - 0 (Wnt-5a Protein)
SB  - IM
MH  - Cell Differentiation/*immunology
MH  - Cell Separation
MH  - Cells, Cultured
MH  - Dendritic Cells/*cytology/immunology/metabolism
MH  - Flow Cytometry
MH  - Fluorescent Antibody Technique
MH  - Humans
MH  - Immune Tolerance/*immunology
MH  - Lymphocyte Activation/immunology
MH  - Lymphocyte Culture Test, Mixed
MH  - Monocytes/*cytology/immunology/metabolism
MH  - Phenotype
MH  - Proto-Oncogene Proteins/*immunology/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/immunology
MH  - Wnt Proteins/*immunology/metabolism
MH  - Wnt-5a Protein
EDAT- 2011/09/16 06:00
MHDA- 2011/11/16 06:00
CRDT- 2011/09/16 06:00
PHST- 2011/09/16 06:00 [entrez]
PHST- 2011/09/16 06:00 [pubmed]
PHST- 2011/11/16 06:00 [medline]
AID - jimmunol.1101243 [pii]
AID - 10.4049/jimmunol.1101243 [doi]
PST - ppublish
SO  - J Immunol. 2011 Oct 15;187(8):4129-39. doi: 10.4049/jimmunol.1101243. Epub 2011 
      Sep 14.