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An A2B Adenosine Receptor Agonist Promotes Th17 Autoimmune Responses in Experimental Autoimmune Uveitis (EAU) via Dendritic Cell Activation.
- Source :
-
PloS one [PLoS One] 2015 Jul 06; Vol. 10 (7), pp. e0132348. Date of Electronic Publication: 2015 Jul 06 (Print Publication: 2015). - Publication Year :
- 2015
-
Abstract
- We have recently reported that, although adenosine receptor (AR) agonists have a suppressive effect on Th1 autoreactive T cells, their effect on Th17 autoreactive T cells and γδ T cells is stimulatory and this effect is mainly mediated via A2A adenosine receptors (A2ARs). In this study, we further demonstrate that treatment of C57BL/6 (B6) mice with a selective A2B adenosine receptor (A2BR) agonist greatly enhanced the development of experimental autoimmune uveitis (EAU), whereas treatment with an A2BR antagonist significantly ameliorated severity of EAU. The A2BR agonist-treated mice showed augmented Th17, but not Th1, responses. Mechanistic studies showed that the A2BR agonist-induced enhancement of the Th17 response was significantly lower when TCR-δ-/- mice received the same treatment and that transfer of γδ T cells into TCR-δ-/- mice partially restored this effect. We also showed that dendritic cells (DCs) from A2BR agonist-treated mice showed a significantly increased ability to activate γδ T cells and Th17 autoreactive T cells. Thus, our previous studies have shown that, in EAU, activated γδ T cells possess greatly increased ability to enhance Th17 autoimmune responses. In the present study, we showed that exposure of DCs to A2BR agonist facilitated γδ T cell activation, leading to augmented Th17 responses and progressive EAU development. Our results further support our previous finding that AR agonists have distinct effects on Th1 and Th17 autoimmune responses.
- Subjects :
- Animals
Autoimmune Diseases genetics
Autoimmune Diseases pathology
Dendritic Cells pathology
Lymphocyte Activation drug effects
Lymphocyte Activation immunology
Mice
Mice, Knockout
Receptor, Adenosine A2B genetics
Receptors, Antigen, T-Cell, gamma-delta genetics
Receptors, Antigen, T-Cell, gamma-delta immunology
Th1 Cells immunology
Th1 Cells pathology
Th17 Cells pathology
Uveitis genetics
Uveitis pathology
Adenosine A2 Receptor Agonists pharmacology
Autoimmune Diseases immunology
Dendritic Cells immunology
Receptor, Adenosine A2B immunology
Th17 Cells immunology
Uveitis immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 10
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 26147733
- Full Text :
- https://doi.org/10.1371/journal.pone.0132348