PMID- 28630103
OWN - NLM
STAT- MEDLINE
DCOM- 20171006
LR  - 20220331
IS  - 1938-3673 (Electronic)
IS  - 0741-5400 (Linking)
VI  - 102
IP  - 3
DP  - 2017 Sep
TI  - Up-regulation of EP(2) and EP(3) receptors in human tolerogenic dendritic cells 
      boosts the immunosuppressive activity of PGE(2).
PG  - 881-895
LID - 10.1189/jlb.2A1216-526R [doi]
AB  - Dendritic cells (DCs) are APCs essential in regulating the immune response. 
      PGE(2), produced during inflammation, has a pivotal role in the maturation of DCs 
      and, therefore, is vital for the immune response. The large variety of biologic 
      functions governed by PGE(2) is mediated by its signaling through 4 distinct 
      E-type prostanoid (EP) receptors. Immunogenic DCs express EP(2) and EP(4), which 
      mediate the PGE(2) signaling. However, the expression and function of EP 
      receptors in human tolerogenic DCs (tol-DCs), which present an inhibitory 
      phenotype, have not yet, to our knowledge, been assessed. To clarify the role of 
      EP receptors in tol-DCs, we examined the expression of different EP receptors and 
      their effect using selective agonists in human cells. We find that EP(2) and 
      EP(3) expression are up-regulated in in vitro-generated tol-DCs compared with 
      mature DCs (mDCs). Activation of EP(2)-EP(4) has a direct effect on the surface 
      expression of costimulatory molecules and maturation receptors, such as CD80, 
      CD83, and CD86 or MHCII and CCR7 in tol-DCs, the latter being exclusively 
      modulated by PGE(2)-EP(4) signaling. Importantly, we find that EP(2) and EP(3) 
      receptors are involved in tolerance induction through IL-10 production by 
      tol-DCs. These results are in sharp contrast with the inflammatory role of EP(4) 
      Moreover, we show that DCs generated in the presence of agonists for EP 
      receptors, induce naive T cell differentiation toward polarized Th1/Th17 cells. 
      Given the differential effects of EP receptors, our results suggest that EP 
      receptor agonist/antagonists might become relevant novel drug templates to 
      modulate immune response.
CI  - (c) Society for Leukocyte Biology.
FAU - Florez-Grau, Georgina
AU  - Florez-Grau G
AD  - Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, 
      Spain.
FAU - Cabezon, Raquel
AU  - Cabezon R
AD  - Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, 
      Spain.
FAU - Borgman, Kyra J E
AU  - Borgman KJE
AD  - ICFO-Institut de Ciencies Fotoniques, Barcelona Institute of Science and 
      Technology, Barcelona, Spain.
FAU - Espana, Carolina
AU  - Espana C
AD  - Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, 
      Spain.
FAU - Lozano, Juan Jose
AU  - Lozano JJ
AD  - Centro de Investigacion Biomedica en Red, Enfermedades Hepaticas y Digestivas 
      (CIBERehd), Barcelona, Spain.
FAU - Garcia-Parajo, Maria F
AU  - Garcia-Parajo MF
AD  - ICFO-Institut de Ciencies Fotoniques, Barcelona Institute of Science and 
      Technology, Barcelona, Spain.
AD  - Insititucio Catalana de Recerca i Estudis Avancats (ICREA), Barcelona, Spain.
FAU - Benitez-Ribas, Daniel
AU  - Benitez-Ribas D
AD  - Centro de Investigacion Biomedica en Red, Enfermedades Hepaticas y Digestivas 
      (CIBERehd), Barcelona, Spain; dbenitezr@clinic.cat.
AD  - Department of Immunology, Hospital Clinic de Barcelona, Barcelona, Spain.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170619
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Antigens, CD)
RN  - 0 (CCR7 protein, human)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (IL10 protein, human)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Receptors, CCR7)
RN  - 0 (Receptors, Prostaglandin E, EP2 Subtype)
RN  - 0 (Receptors, Prostaglandin E, EP3 Subtype)
RN  - 130068-27-8 (Interleukin-10)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Antigens, CD/immunology
MH  - Dendritic Cells/*immunology
MH  - Dinoprostone/*pharmacology
MH  - Histocompatibility Antigens Class II/immunology
MH  - Humans
MH  - Immune Tolerance/*drug effects
MH  - Immunosuppressive Agents/*pharmacology
MH  - Interleukin-10/immunology
MH  - Receptors, CCR7/immunology
MH  - Receptors, Prostaglandin E, EP2 Subtype/*immunology
MH  - Receptors, Prostaglandin E, EP3 Subtype/*immunology
MH  - Th1 Cells/immunology
MH  - Th17 Cells/immunology
OTO - NOTNLM
OT  - EP receptors
OT  - dendritic cells
OT  - immune tolerance
OT  - prostanoid receptors
OT  - signalling
EDAT- 2017/06/21 06:00
MHDA- 2017/10/07 06:00
CRDT- 2017/06/21 06:00
PHST- 2016/12/21 00:00 [received]
PHST- 2017/05/11 00:00 [revised]
PHST- 2017/05/19 00:00 [accepted]
PHST- 2017/06/21 06:00 [pubmed]
PHST- 2017/10/07 06:00 [medline]
PHST- 2017/06/21 06:00 [entrez]
AID - jlb.2A1216-526R [pii]
AID - 10.1189/jlb.2A1216-526R [doi]
PST - ppublish
SO  - J Leukoc Biol. 2017 Sep;102(3):881-895. doi: 10.1189/jlb.2A1216-526R. Epub 2017 
      Jun 19.