PMID- 32112485
OWN - NLM
STAT- MEDLINE
DCOM- 20210119
LR  - 20210119
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 34
IP  - 4
DP  - 2020 Apr
TI  - EP3 signaling in dendritic cells promotes liver repair by inducing IL-13-mediated 
      macrophage differentiation in mice.
PG  - 5610-5627
LID - 10.1096/fj.201901955R [doi]
AB  - Macrophage plasticity is essential for liver wound healing; however, the 
      mechanisms underlying macrophage phenotype switching are largely unknown. 
      Dendritic cells (DCs) are critical initiators of innate immune responses; as 
      such, they orchestrate inflammation following hepatic injury. Here, we subjected 
      EP3-deficient (Ptger3(-/-) ) and wild-type (WT) mice to hepatic 
      ischemia-reperfusion (I/R) and demonstrate that signaling via the prostaglandin E 
      (PGE) receptor EP3 in DCs regulates macrophage plasticity during liver repair. 
      Compared with WT mice, Ptger3(-/-) mice showed delayed liver repair accompanied 
      by reduced expression of hepatic growth factors and accumulation of Ly6C(low) 
      reparative macrophages and monocyte-derived DCs (moDCs). MoDCs were recruited to 
      the boundary between damaged and undamaged liver tissue in an EP3-dependent 
      manner. Adoptive transfer of moDCs from Ptger3(-/-) mice resulted in impaired 
      repair, along with increased numbers of Ly6C(high) inflammatory macrophages. Bone 
      marrow macrophages (BMMs) up-regulated expression of genes related to a 
      reparative macrophage phenotype when co-cultured with moDCs; this phenomenon was 
      dependent on EP3 signaling. In the presence of an EP3 agonist, interleukin 
      (IL)-13 derived from moDCs drove BMMs to increase expression of genes 
      characteristic of a reparative macrophage phenotype. The results suggest that EP3 
      signaling in moDCs facilitates liver repair by inducing IL-13-mediated switching 
      of macrophage phenotype from pro-inflammatory to pro-reparative.
CI  - (c) 2020 Federation of American Societies for Experimental Biology.
FAU - Nakamoto, Shuji
AU  - Nakamoto S
AD  - Department of Molecular Pharmacology, Graduate School of Medical Sciences, 
      Kitasato University, Sagamihara, Japan.
AD  - Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, 
      Japan.
AD  - Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
FAU - Ito, Yoshiya
AU  - Ito Y
AD  - Department of Molecular Pharmacology, Graduate School of Medical Sciences, 
      Kitasato University, Sagamihara, Japan.
AD  - Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, 
      Japan.
FAU - Nishizawa, Nobuyuki
AU  - Nishizawa N
AD  - Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, 
      Japan.
AD  - Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
FAU - Goto, Takuya
AU  - Goto T
AD  - Department of Molecular Pharmacology, Graduate School of Medical Sciences, 
      Kitasato University, Sagamihara, Japan.
AD  - Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, 
      Japan.
AD  - Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
FAU - Kojo, Ken
AU  - Kojo K
AD  - Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
FAU - Kumamoto, Yusuke
AU  - Kumamoto Y
AD  - Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
FAU - Watanabe, Masahiko
AU  - Watanabe M
AD  - Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
FAU - Narumiya, Shuh
AU  - Narumiya S
AD  - Center for Innovation in Immunoregulation Technology and Therapeutics, Kyoto 
      University Graduate School of Medicine, Kyoto, Japan.
FAU - Majima, Masataka
AU  - Majima M
AD  - Department of Molecular Pharmacology, Graduate School of Medical Sciences, 
      Kitasato University, Sagamihara, Japan.
AD  - Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, 
      Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200228
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Interleukin-13)
RN  - 0 (Ptger3 protein, mouse)
RN  - 0 (Receptors, Prostaglandin E, EP3 Subtype)
SB  - IM
MH  - Animals
MH  - *Cell Differentiation
MH  - Dendritic Cells/cytology/*immunology/metabolism
MH  - Interleukin-13/genetics/*metabolism
MH  - Liver Diseases/etiology/pathology/*prevention & control
MH  - Macrophages/*cytology/immunology/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Receptors, Prostaglandin E, EP3 Subtype/*physiology
MH  - Signal Transduction
OTO - NOTNLM
OT  - crosstalk
OT  - immune cells
OT  - ischemia
OT  - prostaglandin
OT  - reperfusion
EDAT- 2020/03/01 06:00
MHDA- 2021/01/20 06:00
CRDT- 2020/03/01 06:00
PHST- 2019/08/02 00:00 [received]
PHST- 2020/01/16 00:00 [revised]
PHST- 2020/02/13 00:00 [accepted]
PHST- 2020/03/01 06:00 [pubmed]
PHST- 2021/01/20 06:00 [medline]
PHST- 2020/03/01 06:00 [entrez]
AID - 10.1096/fj.201901955R [doi]
PST - ppublish
SO  - FASEB J. 2020 Apr;34(4):5610-5627. doi: 10.1096/fj.201901955R. Epub 2020 Feb 28.