PMID- 26030277
OWN - NLM
STAT- MEDLINE
DCOM- 20160324
LR  - 20181113
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 5
DP  - 2015 Jun 1
TI  - The Wnt5a-Ror2 axis promotes the signaling circuit between interleukin-12 and 
      interferon-gamma in colitis.
PG  - 10536
LID - 10.1038/srep10536 [doi]
LID - 10536
AB  - Wnt5a, which regulates various cellular functions in Wnt signaling, is involved 
      in inflammatory responses, however the mechanism is not well understood. We 
      examined the role of Wnt5a signaling in intestinal immunity using conditional 
      knockout mice for Wnt5a and its receptor Ror2. Removing Wnt5a or Ror2 in adult 
      mice suppressed dextran sodium sulfate (DSS)-induced colitis. It also attenuated 
      the DSS-dependent increase in inflammatory cytokine production and decreased 
      interferon-gamma (IFN-gamma)-producing CD4(+) Th1 cell numbers in the colon. Wnt5a was 
      highly expressed in stromal fibroblasts in ulcerative lesions in the DSS-treated 
      mice and inflammatory bowel disease patients. Dendritic cells (DCs) isolated from 
      the colon of Wnt5a and Ror2 deficient mice reduced the ability to differentiate 
      naive CD4(+) T cells to IFN-gamma-producing CD4(+) Th1 cells. In vitro experiments 
      demonstrated that the Wnt5a-Ror2 signaling axis augmented the DCs priming effect 
      of IFN-gamma, leading to enhanced lipopolysaccharide (LPS)-induced interleukin 
      (IL)-12 expression. Taken together, these results suggest that Wnt5a promotes 
      IFN-gamma signaling, leading to IL-12 expression in DCs, and thereby inducing Th1 
      differentiation in colitis.
FAU - Sato, Akira
AU  - Sato A
AD  - Departments of Molecular Biology and Biochemistry.
FAU - Kayama, Hisako
AU  - Kayama H
AD  - Microbiology and Immunology, and.
FAU - Shojima, Kensaku
AU  - Shojima K
AD  - Departments of Molecular Biology and Biochemistry.
FAU - Matsumoto, Shinji
AU  - Matsumoto S
AD  - Departments of Molecular Biology and Biochemistry.
FAU - Koyama, Hirofumi
AU  - Koyama H
AD  - Departments of Molecular Biology and Biochemistry.
FAU - Minami, Yasuhiro
AU  - Minami Y
AD  - Department of Physiology and Cell Biology, Graduate School of Medicine, Kobe 
      University, 7-5-1 Kusunoki-cho, Chuoh-ku, Kobe 650-0017, Japan.
FAU - Nojima, Satoshi
AU  - Nojima S
AD  - Pathology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita 
      565-0871, Japan.
FAU - Morii, Eiichi
AU  - Morii E
AD  - Pathology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita 
      565-0871, Japan.
FAU - Honda, Hiroaki
AU  - Honda H
AD  - Department of Disease Model, Research Institute of Radiation Biology and 
      Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, 
      Japan.
FAU - Takeda, Kiyoshi
AU  - Takeda K
AD  - Microbiology and Immunology, and.
FAU - Kikuchi, Akira
AU  - Kikuchi A
AD  - Departments of Molecular Biology and Biochemistry.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150601
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (RNA, Messenger)
RN  - 0 (Wnt Proteins)
RN  - 0 (Wnt-5a Protein)
RN  - 0 (Wnt5a protein, mouse)
RN  - 187348-17-0 (Interleukin-12)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 9042-14-2 (Dextran Sulfate)
RN  - EC 2.7.10.1 (Receptor Tyrosine Kinase-like Orphan Receptors)
RN  - EC 2.7.10.1 (Ror2 protein, mouse)
SB  - IM
MH  - Animals
MH  - Bone Marrow/metabolism
MH  - Colitis/chemically induced/genetics/*metabolism
MH  - Cytokines/metabolism
MH  - Dendritic Cells/immunology/metabolism
MH  - Dextran Sulfate/adverse effects
MH  - Disease Models, Animal
MH  - Disease Susceptibility
MH  - Fibroblasts/metabolism
MH  - Gene Expression
MH  - Inflammation Mediators/metabolism
MH  - Interferon-gamma/*metabolism
MH  - Interleukin-12/*metabolism
MH  - Intestinal Mucosa/metabolism/pathology
MH  - Mice
MH  - Mice, Knockout
MH  - Organ Specificity/genetics
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptor Tyrosine Kinase-like Orphan Receptors/genetics/*metabolism
MH  - *Signal Transduction
MH  - Wnt Proteins/genetics/*metabolism
MH  - Wnt-5a Protein
PMC - PMC4450756
EDAT- 2015/06/02 06:00
MHDA- 2016/03/25 06:00
PMCR- 2015/06/01
CRDT- 2015/06/02 06:00
PHST- 2014/12/09 00:00 [received]
PHST- 2015/04/23 00:00 [accepted]
PHST- 2015/06/02 06:00 [entrez]
PHST- 2015/06/02 06:00 [pubmed]
PHST- 2016/03/25 06:00 [medline]
PHST- 2015/06/01 00:00 [pmc-release]
AID - srep10536 [pii]
AID - 10.1038/srep10536 [doi]
PST - epublish
SO  - Sci Rep. 2015 Jun 1;5:10536. doi: 10.1038/srep10536.