PMID- 38088451
OWN - NLM
STAT- MEDLINE
DCOM- 20240318
LR  - 20240318
IS  - 1521-4141 (Electronic)
IS  - 0014-2980 (Linking)
VI  - 54
IP  - 3
DP  - 2024 Mar
TI  - PGE2-EP4 signaling steers cDC2 maturation toward the induction of suppressive 
      T-cell responses.
PG  - e2350770
LID - 10.1002/eji.202350770 [doi]
AB  - Dendritic cells (DCs) shape adaptive immunity in response to environmental cues 
      such as cytokines or lipid mediators, including prostaglandin E2 (PGE2). In 
      cancer, tumors are known to establish an enriched PGE2 microenvironment. 
      Tumor-derived PGE2 primes regulatory features across immune cells, including DCs, 
      facilitating tumor progression. PGE2 shapes DC function by providing signaling 
      via its two so-called E-prostanoid receptors (EPs) EP2 and EP4. Although studies 
      with monocyte-derived DCs have shown the importance of PGE2 signaling, the role 
      of PGE2-EP2/EP4 on conventional DCs type 2 (cDC2s), is still poorly defined. In 
      this study, we investigated the function of EP2 and EP4 using specific EP 
      antagonists on human cDC2s. Our results show that EP2 and EP4 exhibit different 
      functions in cDC2s, with EP4 modulating the upregulation of activation markers 
      (CD80, CD86, CD83, MHC class II) and the production of IL-10 and IL-23. 
      Furthermore, PGE2-EP4 boosts CCR type 7-based migration as well as a higher 
      T-cell expansion capacity, characterized by the enrichment of suppressive rather 
      than pro-inflammatory T-cell populations. Our findings are relevant to further 
      understanding the role of EP receptors in cDC2s, underscoring the benefit of 
      targeting the PGE2-EP2/4 axis for therapeutic purposes in diseases such as 
      cancer.
CI  - (c) 2024 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.
FAU - Cuenca-Escalona, Jorge
AU  - Cuenca-Escalona J
AUID- ORCID: 0000-0002-4915-1518
AD  - Department of Medical BioSciences, Radboud University Medical Center, Geert 
      Grooteplein Zuid 26-28, Nijmegen, 6525GA, the Netherlands.
FAU - Florez-Grau, Georgina
AU  - Florez-Grau G
AD  - Department of Medical BioSciences, Radboud University Medical Center, Geert 
      Grooteplein Zuid 26-28, Nijmegen, 6525GA, the Netherlands.
FAU - van den Dries, Koen
AU  - van den Dries K
AD  - Department of Medical BioSciences, Radboud University Medical Center, Geert 
      Grooteplein Zuid 26-28, Nijmegen, 6525GA, the Netherlands.
FAU - Cambi, Alessandra
AU  - Cambi A
AD  - Department of Medical BioSciences, Radboud University Medical Center, Geert 
      Grooteplein Zuid 26-28, Nijmegen, 6525GA, the Netherlands.
FAU - de Vries, I Jolanda M
AU  - de Vries IJM
AD  - Department of Medical BioSciences, Radboud University Medical Center, Geert 
      Grooteplein Zuid 26-28, Nijmegen, 6525GA, the Netherlands.
LA  - eng
GR  - LSHM18056-SGF/Health Holland grant DC4Balance/
PT  - Journal Article
DEP - 20240108
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - K7Q1JQR04M (Dinoprostone)
RN  - 0 (Receptors, Prostaglandin E, EP2 Subtype)
RN  - 0 (Receptors, Prostaglandin E, EP4 Subtype)
SB  - IM
MH  - Humans
MH  - *Dinoprostone
MH  - T-Lymphocytes
MH  - Receptors, Prostaglandin E, EP2 Subtype
MH  - Receptors, Prostaglandin E, EP4 Subtype
MH  - *Neoplasms
MH  - Tumor Microenvironment
OTO - NOTNLM
OT  - Conventional dendritic cells type 2
OT  - Dendritic cells
OT  - E-prostanoid receptor
OT  - Immune responses
OT  - Innate immunity
OT  - Prostaglandin E2
OT  - Signal transduction
OT  - T cells
OT  - Tumor microenvironment
EDAT- 2023/12/13 12:44
MHDA- 2024/03/18 06:44
CRDT- 2023/12/13 08:59
PHST- 2023/12/11 00:00 [revised]
PHST- 2023/09/12 00:00 [received]
PHST- 2023/12/12 00:00 [accepted]
PHST- 2024/03/18 06:44 [medline]
PHST- 2023/12/13 12:44 [pubmed]
PHST- 2023/12/13 08:59 [entrez]
AID - 10.1002/eji.202350770 [doi]
PST - ppublish
SO  - Eur J Immunol. 2024 Mar;54(3):e2350770. doi: 10.1002/eji.202350770. Epub 2024 Jan 
      8.