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

BioRxiv : the Preprint Server for Biology
Karin SchaeubleSanjiv A Luther

Abstract

Fibroblastic reticular cells (FRC) of lymphoid T zones actively promote T cell trafficking, homeostasis and expansion, but can also attenuate excessive T cell responses via inducible nitric oxide and constitutive prostanoid release. It has remained unclear under which conditions these FRC-derived mediators can dampen T cell responses and whether this occurs in vivo. Here we confirm that murine lymph node FRC 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 nitric oxide which only comes into play during strong T cell responses. In chronic infections in vivo, PGE2-receptor signaling in virus-specific CD8 T cells was shown by others to suppress T cell survival and function. Using CCL19cre x COX2flox/flox mice we now identify CCL19cre+ FRC as the critical source of this COX2-dependent suppressive factor, suggesting PGE2-expressing FRC within lymphoid tissues are an interesting therapeutic target to improve T cell mediated pathogen control during chronic infection.

Related Concepts

Cell Growth
Factor X
Fibroblasts
Inflammation
Lymph Nodes
Lymphoid Tissue
Laboratory mice
Nitric Oxide
Physiological Aspects
Prostaglandins

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