title: Activation of the adenosine A2A receptor attenuates experimental autoimmune myasthenia gravis severity.
abstract: The adenosine A2A receptor (A2AR) is the major cellular adenosine receptor commonly associated with immunosuppression. Here, we investigated whether A2AR activation holds the potential for impacting the severity of experimental autoimmune myasthenia gravis (EAMG) induced following immunization of Lewis rats with the acetylcholine receptor (AChR) R97-116 peptide. This report demonstrates reduced A2AR expression by both T cells and B cells residing in spleen and lymph nodes following EAMG induction. A2AR stimulation inhibited anti-AChR antibody production and proliferation of AChR-specific lymphocytes in vitro. Inhibition was blocked with the A2AR antagonists or protein kinase A inhibitor. We also determined that the development of EAMG was accompanied by a T-helper cell imbalance that could be restored following A2AR stimulation that resulted in increased Treg cell levels and a reduction in Th1-, Th2-, and Th17-cell subtypes. An EAMG-preventive treatment regimen was established that consisted of (2-(p-(2-carbonylethyl)phenylethylamino)-5-N-ethylcarboxamidoadenosine) (CGS21680; A2AR agonist) administration 1 day prior to EAMG induction. Administration of CGS21680 29 days post EAMG induction (therapeutic treatment) also ameliorated disease severity. We conclude that A2AR agonists may represent a new class of compounds that can be developed for use in the treatment of myasthenia gravis or other T-cell- and B-cell-mediated autoimmune diseases.
authors.affiliation: Department of Neurobiology, Harbin Medical University Provincial Key Lab of Neurobiology, Harbin Medical University, Heilongjiang, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Lili
authors.initials: L
authors.lastname: Mu
authors.forename: Jinghua
authors.initials: J
authors.lastname: Wang
authors.forename: Jia
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Xie
authors.forename: Qingfei
authors.initials: Q
authors.lastname: Kong
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Yao
authors.forename: Yumei
authors.initials: Y
authors.lastname: Liu
authors.forename: Lihua
authors.initials: L
authors.lastname: Wang
authors.forename: Guangyou
authors.initials: G
authors.lastname: Wang
authors.forename: Dandan
authors.initials: D
authors.lastname: Wang
authors.forename: Lianhong
authors.initials: L
authors.lastname: Jin
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.forename: Hulun
authors.initials: H
authors.lastname: Li
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D058908:Adenosine A2 Receptor Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D005260:Female; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology*; D010627:Phenethylamines / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000276:immunology; D012720:Severity of Illness Index; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D057134:Antibodies, Neutralizing; D010627:Phenethylamines; D043705:Receptor, Adenosine A2A; D011950:Receptors, Cholinergic; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D000241:Adenosine