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

Details

Serval ID
serval:BIB_6C21F8646A14
Type
Article: article from journal or magazin.
Collection
Publications
Title
Attenuation of chronic antiviral T-cell responses through constitutive COX2-dependent prostanoid synthesis by lymph node fibroblasts.
Journal
PLoS biology
Author(s)
Schaeuble K., Cannelle H., Favre S., Huang H.Y., Oberle S.G., Speiser D.E., Zehn D., Luther S.A.
ISSN
1545-7885 (Electronic)
ISSN-L
1544-9173
Publication state
Published
Issued date
07/2019
Peer-reviewed
Oui
Volume
17
Number
7
Pages
e3000072
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
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.
Keywords
Animals, Cell Line, Cell Movement/genetics, Cell Movement/immunology, Cell Proliferation/genetics, Cyclooxygenase 2/genetics, Cyclooxygenase 2/immunology, Cyclooxygenase 2/metabolism, Fibroblasts/immunology, Fibroblasts/metabolism, Fibroblasts/virology, Lymph Nodes/cytology, Lymph Nodes/immunology, Lymph Nodes/metabolism, Lymphocyte Activation/immunology, Lymphocytic Choriomeningitis/immunology, Lymphocytic Choriomeningitis/metabolism, Lymphocytic Choriomeningitis/virology, Lymphocytic choriomeningitis virus/immunology, Lymphocytic choriomeningitis virus/physiology, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Prostaglandins/biosynthesis, Prostaglandins/immunology, T-Lymphocytes/immunology, T-Lymphocytes/virology
Pubmed
Web of science
Open Access
Yes
Funding(s)
Swiss National Science Foundation / 31003A-166161
Create date
22/07/2019 17:15
Last modification date
30/01/2020 7:20
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