Attenuation of chronic antiviral T-cell responses through constitutive COX2-dependent prostanoid synthesis by lymph node fibroblasts

Détails

ID Serval
serval:BIB_6C21F8646A14
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Attenuation of chronic antiviral T-cell responses through constitutive COX2-dependent prostanoid synthesis by lymph node fibroblasts
Périodique
PLoS biology
Auteur(s)
Schaeuble Karin, Cannelle Hélène, Favre Stéphanie, Huang Hsin-Ying, Oberle Susanne G., Speiser Daniel E., Zehn Dietmar, Luther Sanjiv A.
ISSN
1545-7885 (Electronic)
ISSN-L
1544-9173
Statut éditorial
Publié
Date de publication
15/07/2019
Peer-reviewed
Oui
Volume
17
Numéro
7
Pages
e3000072
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
Lymphoid T-zone fibroblastic reticular cells (FRCs) actively promote T-cell trafficking, homeostasis, and expansion but can also attenuate excessive T-cell responses via inducible nitric oxide (NO) and constitutive prostanoid release. It remains unclear how these FRC-derived mediators dampen T-cell responses and whether this occurs in vivo. Here, we confirm that murine lymph node (LN) FRCs produce prostaglandin E2 (PGE2) in a cyclooxygenase-2 (COX2)-dependent and inflammation-independent fashion. We show that this COX2/PGE2 pathway is active during both strong and weak T-cell responses, in contrast to NO, which only comes into play during strong T-cell responses. During chronic infections in vivo, PGE2-receptor signaling in virus-specific cluster of differentiation (CD)8 cytotoxic T cells was shown by others to suppress T-cell survival and function. Using COX2flox/flox mice crossed to mice expressing Cre recombinase expression under control of the CC chemokine ligand (CCL19) promoter (CCL19cre), we now identify CCL19+ FRC as the critical source of this COX2-dependent suppressive factor, suggesting PGE2-expressing FRCs within lymphoid tissues are an interesting therapeutic target to improve T-cell-mediated pathogen control during chronic infection.
Pubmed
Web of science
Open Access
Oui
Financement(s)
Fonds national suisse / 31003A-166161
Création de la notice
22/07/2019 16:15
Dernière modification de la notice
21/09/2019 5:08
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