TLR-Induced IL-12 and CCL2 Production by Myeloid Cells Is Dependent on Adenosine A3 Receptor-Mediated Signaling

The Journal of Immunology : Official Journal of the American Association of Immunologists
Céline van der PuttenJeffrey J Bajramovic

Abstract

TLR-induced signaling potently activates cells of the innate immune system and is subject to regulation at different levels. Inflammatory conditions are associated with increased levels of extracellular adenosine, which can modulate TLR-induced production of cytokines through adenosine receptor-mediated signaling. There are four adenosine receptor subtypes that induce different signaling cascades. In this study, we demonstrate a pivotal contribution of adenosine A3 receptor (A3R)-mediated signaling to the TLR4-induced expression of IL-12 in different types of human myeloid APC. In dendritic cells, IL-12 and CCL2 responses as evoked by TLR2, 3, 4, 5, and 8, as well as IL-12 responses evoked by whole pathogens, were all reduced when A3R-mediated signaling was blocked. As a result, concomitant production of IFN-γ and IL-17 by T cells was significantly inhibited. We further show that selective inhibition of A3R-mediated signaling reduced TLR-induced phosphorylation of the transcription factor STAT1 at tyrosine 701. Next-generation sequencing revealed that A3R-mediated signaling controls the expression of metallothioneins, known inhibitors of STAT1 phosphorylation. Together our results reveal a novel regulatory layer of innate immun...Continue Reading

References

Nov 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·C A SalvatoreR G Johnson
Aug 29, 1996·European Journal of Pharmacology·C D McWhinneyC K Edwards
Dec 22, 1999·The Journal of Immunology : Official Journal of the American Association of Immunologists·A A LinkI J Elenkov
Oct 12, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·G HaskóC Szabó
Sep 5, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·E PantherJ Norgauer
Feb 28, 2002·Annual Review of Immunology·Charles A Janeway, Ruslan Medzhitov
Jul 12, 2002·Journal of Cellular Biochemistry·Masako KanekiyoKeiichi Tanaka
Jan 14, 2003·Annual Review of Immunology·Kiyoshi TakedaShizuo Akira
Oct 4, 2003·Journal of Leukocyte Biology·Kate SchroderDavid A Hume
May 4, 2004·Nature Reviews. Molecular Cell Biology·Lin-Feng Chen, Warner C Greene
Jul 2, 2004·Nature Reviews. Immunology·Shizuo Akira, Kiyoshi Takeda
Sep 30, 2004·Nature Immunology·Akiko Iwasaki, Ruslan Medzhitov
Jan 12, 2005·Arthritis Research & Therapy·Taro Kawai, Shizuo Akira
Aug 24, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Andrea la SalaBrian L Kelsall
Nov 23, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·J Michelle KahlenbergGeorge R Dubyak
Mar 7, 2006·Nature Reviews. Drug Discovery·Kenneth A Jacobson, Zhan-Guo Gao
Aug 8, 2006·Nature Immunology·Hidemitsu KitamuraToshio Hirano
Nov 21, 2007·British Journal of Pharmacology·T M Palmer, M A Trevethick
Dec 7, 2007·Annals of the New York Academy of Sciences·Eugenio MocchegianiMarco Malavolta
May 27, 2008·Advances in Immunology·Toshio HiranoTomoyuki Suzuki
Apr 30, 2009·Annual Review of Nutrition·Hajo Haase, Lothar Rink
Jun 6, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Céline van der PuttenJeffrey J Bajramovic
May 1, 2013·Proceedings of the National Academy of Sciences of the United States of America·Chuan WuVijay K Kuchroo
Jun 28, 2013·BioFactors·Hajo Haase, Lothar Rink
Jan 5, 2014·PLoS Pathogens·Kavitha Subramanian VigneshGeorge S Deepe
Apr 17, 2015·Current Opinion in Immunology·Nathalie Schmitt, Hideki Ueno
Mar 10, 2016·International Journal of Molecular Sciences·Tomoki Kimura, Taiho Kambe
Jul 29, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mariam Mathew GeorgeGeorge S Deepe
Oct 14, 2017·International Reviews of Immunology·Mallenahally Kusha VidyaRaghavendra Bhatta
Oct 27, 2017·International Journal of Molecular Sciences·Kavitha Subramanian Vignesh, George S Deepe

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

© 2022 Meta ULC. All rights reserved