Adenosine, through the A1 receptor, inhibits vesicular MHC class I cross-presentation by resting DC

Molecular Immunology
Liying ChenMikael Jondal

Abstract

Levels of the purine nucleoside adenosine (Ado) increase during conditions related to hypoxia such as inflammation, tissue damage and cancer. Ado binds to a set of G protein-linked receptors (A(1), A(2A), A(2B) and A(3)) which are widely and differentially expressed in tissues and regulate inflammatory and autoimmune responses. We have investigated the effect of the stable Ado analogue 2-Chloro-Adenosine (2-Cl-Ado) on vesicular MHC class I cross-presentation using the exogenous protein ovalbumin (OVA) and cultured mouse dendritic cells (DC) at different stages of maturation and activation. 2-Cl-Ado was found to strongly inhibit cross-presentation of OVA by resting DC (rDC) but had a much smaller effect on immature and CpG-activated DC. The effect of Ado on rDC could be fully reversed by the Ado receptor antagonist CGS 15943 and by pertussis toxin demonstrating that it was mediated by a Gi-linked Ado receptor. A(1) Ado receptor mRNA was found to be upregulated in rDC and, by using rDC from A(1), A(2A) and A(3) receptor knockout mice, this receptor was found to mediate most of the suppression. 2-Cl-Ado did not influence the cellular uptake of OVA, the cytosolic processing of the protein in rDC or the formation of intracellular MH...Continue Reading

Citations

Apr 26, 2014·Thrombosis and Haemostasis·P AdamskiJ Kubica
Oct 31, 2009·Scandinavian Journal of Immunology·L Chen, M Jondal
Aug 26, 2016·Purinergic Signalling·Martha de Oliveira BravoFelipe Saldanha-Araujo
Oct 15, 2008·International Reviews of Immunology·Christopher C Fraser
Apr 25, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jeffrey H MillsMargaret S Bynoe
Mar 18, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sabine RingKarsten Mahnke

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