Activation of the adenosine A2A receptor attenuates experimental autoimmune myasthenia gravis severity

European Journal of Immunology

Volumn 42, Issue 5, 2012, Pages 1140-1151

  Li, Na ^a   Mu, Lili ^a   Wang, Jinghua ^a   Zhang, Jia ^a   Xie, Xiaoli ^a   Kong, Qingfei ^a   Tang, Wei ^a   Yao, Xiuhua ^a   Liu, Yumei ^a   Wang, Lihua ^a   Wang, Guangyou ^a   Wang, Dandan ^a   Jin, Lianhong ^a   Sun, Bo ^a   Li, Hulun ^a,b  

^a HARBIN MEDICAL UNIVERSITY   (China)

^b Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment   (China)

Author keywords

A2AR; AChR; Autoimmune disease; EAMG; Th subsets

Indexed keywords

2 [4 (2 CARBOXYETHYL)PHENETHYLAMINO]ADENOSINE 5' (N ETHYLCARBOXAMIDE); ADENOSINE A2A RECEPTOR; ADENOSINE A2A RECEPTOR ANTAGONIST; CHOLINERGIC RECEPTOR; CHOLINERGIC RECEPTOR ANTIBODY; CYCLIC AMP DEPENDENT PROTEIN KINASE INHIBITOR; IMMUNOGLOBULIN G ANTIBODY;

ANIMAL CELL; ANIMAL MODEL; ANTIBODY BLOOD LEVEL; ANTIBODY PRODUCTION; ARTICLE; ATTENUATION; B LYMPHOCYTE; CONTROLLED STUDY; DISEASE SEVERITY; DRUG EFFECT; ENZYME LINKED IMMUNOSORBENT ASSAY; EX VIVO STUDY; FEMALE; HELPER CELL; IMMUNIZATION; LYMPH NODE; LYMPHOCYTE PROLIFERATION; MYASTHENIA GRAVIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; RAT; REGULATORY T LYMPHOCYTE; SPLEEN; T LYMPHOCYTE; TH1 CELL; TH17 CELL; TH2 CELL;

ADENOSINE; ADENOSINE A2 RECEPTOR AGONISTS; ADENOSINE A2 RECEPTOR ANTAGONISTS; ANIMALS; ANTIBODIES, NEUTRALIZING; B-LYMPHOCYTES; FEMALE; LYMPH NODES; LYMPHOCYTE ACTIVATION; MYASTHENIA GRAVIS, AUTOIMMUNE, EXPERIMENTAL; PHENETHYLAMINES; RATS; RATS, INBRED LEW; RECEPTOR, ADENOSINE A2A; RECEPTORS, CHOLINERGIC; SEVERITY OF ILLNESS INDEX; SPLEEN; T-LYMPHOCYTES;

EID: 84860340468     PISSN: 00142980     EISSN: 15214141     Source Type: Journal    
DOI: 10.1002/eji.201142088     Document Type: Article

References (38)

1. Zuckerman, N. S., Howard, W. A., Bismuth, J., Gibson, K., Edelman, H., Berrih-Aknin, S., Dunn-Walters, D. et al., Ectopic GCin the thymus of myasthenia gravis patients show characteristics of normal GC. Eur. J. Immunol. 2010. 40: 1150-1161.
2. Vincent, A., Unravelling the pathogenesis of myasthenia gravis. Nat. Rev. Immunol. 2002. 2: 797-804.
3. Dwyer, D. S., Bradley, R. J., Urquhart, C. K. and Kearney, J. F., Naturally occurring anti-idiotypic antibodies in myasthenia gravis patients. Nature 1983. 301: 611-614.
4. Baggi, F., Annoni, A., Ubiali, F., Milani, M., Longhi, R., Scaioli, W., Cornelio, F. et al., Breakdown of tolerance to a self-peptide of acetylcholine receptor alpha-subunit induces experimental myasthenia gravis in rats. J. Immunol. 2004. 172: 2697-2703.
5. Balasa, B., Deng, C., Lee, J., Bradley, L. M., Dalton, D. K., Christadoss, P. and Sarvetnick, N., Interferon gamma (IFN-gamma) is necessary for the genesis of acetylcholine receptor-induced clinical experimental autoimmune myasthenia gravis in mice. J. Exp. Med. 1997. 186: 385-391.
6. Wang, W., Ostlie, N. S., Conti-Fine, B. M. and Milani, M., The susceptibility to experimental myasthenia gravis of STAT6-/- and STAT4-/- BALB/c mice suggests a pathogenic role of Th1 cells. J. Immunol. 2004. 172: 97-103.
7. Moiola, L., Galbiati, F., Martino, G., Amadio, S., Brambilla, E., Comi, G., Vincent, A. et al., IL-12 is involved in the induction of experimental autoimmune myasthenia gravis, an antibody-mediated disease. Eur. J. Immunol. 1998. 28: 2487-2497.
8. Wang, W., Milani, M., Ostlie, N., Okita, D., Agarwal, R. K., Caspi, R. R. and Conti-Fine, B. M., C57BL/6 mice genetically deficient in IL-12/IL-23 and IFN-gamma are susceptible to experimental autoimmune myasthenia gravis, suggesting a pathogenic role of non-Th1 cells. J. Immunol. 2007. 178: 7072-7080.
9. Milani, M., Ostlie, N., Wang, W. and Conti-Fine, B. M., T cells and cytokines in the pathogenesis of acquired myasthenia gravis. Ann. N. Y. Acad. Sci. 2003. 998: 284-307.
10. Balandina, A., Lecart, S., Dartevelle, P., Saoudi, A. and Berrih-Aknin, S., Functional defect of regulatory CD4(+)CD25+ T cells in the thymus of patients with autoimmune myasthenia gravis. Blood 2005. 105: 735-741.
11. Liu, R., Zhou, Q., La Cava, A., Campagnolo, D. I., Van Kaer, L. and Shi, F. D., Expansion of regulatory T cells via IL-2/anti-IL-2 mAb complexes suppresses experimental myasthenia. Eur. J. Immunol. 2010. 40: 1577-1589.
12. Ivanov, II, McKenzie, B. S., Zhou, L., Tadokoro, C. E., Lepelley, A., Lafaille, J. J., Cua, D. J. et al., The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 2006. 126: 1121-1133.
13. Huh, J. R., Leung, M. W., Huang, P., Ryan, D. A., Krout, M. R., Malapaka, R. R., Chow, J. et al., Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORgammat activity. Nature 2011. 472: 486-490.
14. Mu, L., Sun, B., Kong, Q., Wang, J., Wang, G., Zhang, S., Wang, D. et al., Disequilibrium of T helper type 1, 2 and 17 cells and regulatory T cells during the development of experimental autoimmune myasthenia gravis. Immunology 2009. 128: e826-836.
15. Ohta, A. and Sitkovsky, M., Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage. Nature 2001. 414: 916-920.
16. Sitkovsky, M. V., Lukashev, D., Apasov, S., Kojima, H., Koshiba, M., Caldwell, C., Ohta, A. et al., Physiological control of immune response and inflammatory tissue damage by hypoxia-inducible factors and adenosine A2A receptors. Annu. Rev. Immunol. 2004. 22: 657-682.
17. Yu, L., Huang, Z., Mariani, J., Wang, Y., Moskowitz, M. and Chen, J. F., Selective inactivation or reconstitution of adenosine A2A receptors in bone marrow cells reveals their significant contribution to the development of ischemic brain injury. Nat. Med. 2004. 10: 1081-1087.
18. Hasko, G., Linden, J., Cronstein, B. and Pacher, P., Adenosine receptors: therapeutic aspects for inflammatory and immune diseases. Nat. Rev. Drug Discov. 2008. 7: 759-770.
19. Koshiba, M., Rosin, D. L., Hayashi, N., Linden, J. and Sitkovsky, M. V., Patterns of A2A extracellular adenosine receptor expression in different functional subsets of human peripheral T cells. Flow cytometry studies with anti-A2A receptor monoclonal antibodies. Mol. Pharmacol. 1999. 55: 614-624.
20. Lukashev, D. E., Smith, P. T., Caldwell, C. C., Ohta, A., Apasov, S. G. and Sitkovsky, M. V., Analysis of A2a receptor-deficient mice reveals no significant compensatory increases in the expression of A2b, A1, and A3 adenosine receptors in lymphoid organs. Biochem. Pharmacol. 2003. 65: 2081-2090.
21. Mandler, R., Birch, R. E., Polmar, S. H., Kammer, G. M. and Rudolph, S. A., Abnormal adenosine-induced immunosuppression and cAMP metabolism in T lymphocytes of patients with systemic lupus erythematosus. Proc. Natl. Acad. Sci. USA 1982. 79: 7542-7546.
22. Ramlackhansingh, A. F., Bose, S. K., Ahmed, I., Turkheimer, F. E., Pavese, N. and Brooks, D. J., Adenosine 2A receptor availability in dyskinetic and nondyskinetic patients with Parkinson disease. Neurology 2011. 76: 1811-1816.
23. Mills, J. H., Thompson, L. F., Mueller, C., Waickman, A. T., Jalkanen, S., Niemela, J., Airas, L. and Bynoe, M. S., CD73 is required for efficient entry of lymphocytes into the central nervous system during experimental autoimmune encephalomyelitis. Proc. Nat. Acad. Sci. USA 2008. 105: 9325-9330.
24. Niemela, J., Ifergan, I., Yegutkin, G. G., Jalkanen, S., Prat, A. and Airas, L., IFN-beta regulates CD73 and adenosine expression at the blood-brain barrier. Eur. J. Immunol. 2008. 38: 2718-2726.
25. Hider, S. L., Thomson, W., Mack, L. F., Armstrong, D. J., Shadforth, M. and Bruce, I. N., Polymorphisms within the adenosine receptor 2a gene are associated with adverse events in RA patients treated with MTX. Rheumatology (Oxford) 2008. 47: 1156-1159.
26. Sevigny, C. P., Li, L., Awad, A. S., Huang, L., McDuffie, M., Linden, J., Lobo, P. I. et al., Activation of adenosine 2A receptors attenuates allograft rejection and alloantigen recognition. J. Immunol. 2007. 178: 4240-4249.
27. Dal Ponte, C., Alchera, E., Follenzi, A., Imarisio, C., Prat, M., Albano, E. and Carini, R., Pharmacological postconditioning protects against hepatic ischemia/reperfusion injury. Liver Transpl. 2011. 17: 474-482.
28. Lappas, C. M., Rieger, J. M. and Linden, J., A2A adenosine receptor induction inhibits IFN-gamma production in murine CD4+ T cells. J. Immunol. 2005. 174: 1073-1080.
29. Hoskin, D. W., Butler, J. J., Drapeau, D., Haeryfar, S. M. and Blay, J., Adenosine acts through an A3 receptor to prevent the induction of murine anti-CD3-activated killer T cells. Int. J. Cancer 2002. 99: 386-395.
30. Zhang, G. X., Navikas, V. and Link, H., Cytokines and the pathogenesis of myasthenia gravis. Muscle Nerve 1997. 20: 543-551.
31. Fredholm, B. B., Chern, Y., Franco, R. and Sitkovsky, M., Aspects of the general biology of adenosine A2A signaling. Prog. Neurobiol. 2007. 83: 263-276.
32. Huang, S., Apasov, S., Koshiba, M. and Sitkovsky, M., Role of A2A extracellular adenosine receptor-mediated signaling in adenosine-mediated inhibition of T-cell activation and expansion. Blood 1997. 90: 1600-1610.
33. Zarek, P. E., Huang, C. T., Lutz, E. R., Kowalski, J., Horton, M. R., Linden, J., Drake, C. G. et al., A2A receptor signaling promotes peripheral tolerance by inducing T-cell anergy and the generation of adaptive regulatory T cells. Blood 2008. 111: 251-259.
34. Ohta, A., Ohta, A., Madasu, M., Kini, R., Subramanian, M., Goel, N. and Sitkovsky, M., A2A adenosine receptor may allow expansion of T cells lacking effector functions in extracellular adenosine-rich microenvironments. J. Immunol. 2009. 183: 5487-5493.
35. Csoka, B., Himer, L., Selmeczy, Z., Vizi, E. S., Pacher, P., Ledent, C., Deitch, E. A., et al., Adenosine A2A receptor activation inhibits T helper 1 and T helper 2 cell development and effector function. FASEB J. 2008. 22: 3491-3499.
36. Oh, S., Rankin, A. L. and Caton, A. J., CD4+CD25+ regulatory T cells in autoimmune arthritis. Immunol. Rev. 2011. 233: 97-111.
37. Kong, Q. F., Sun, B., Wang, G. Y., Zhai, D. X., Mu, L. L., Wang, D. D., Wang, J. H., et al., BM stromal cells ameliorate experimental autoimmune myasthenia gravis by altering the balance of Th cells through the secretion of IDO. Eur. J. Immunol. 2009. 39: 800-809.
38. Dong, C., Diversification of T-helper-cell lineages: finding the family root of IL-17-producing cells. Nat. Rev. Immunol. 2006. 6: 329-333.