Rapamycin ameliorates experimental autoimmune uveoretinitis by inhibiting Th1/Th2/Th17 cells and upregulating CD4+CD25+ Foxp3 regulatory T cells

International Journal of Ophthalmology

Volumn 8, Issue 4, 2015, Pages 659-664

  Yuan, Li Fei ^a,b   Li, Guang Da ^a,c   Ren, Xin Jun ^a   Nian, Hong ^a   Li, Xiao Rong ^a   Zhang, Xiao Min ^a  

^a TIANJIN MEDICAL UNIVERSITY   (China)

^b Hebei Key Laboratory of Ophthalmology   (China)

^c LINYI PEOPLE'S HOSPITAL   (China)

Author keywords

Experimental autoimmune uveoretinitis; Rapamycin; Regulatory T cells; Th1 cells; Th17 cells; Th2 cells; Uveitis

Indexed keywords

EID: 84938597826     PISSN: 22223959     EISSN: 22274898     Source Type: Journal    
DOI: 10.3980/j.issn.2222-3959.2015.04.03     Document Type: Article

References (38)

1. Caspi RR. Experimental autoimmune uveoretinitis in the rat and mouse. Curr Protoc Immunol 2003;Chapter 15:Unit 15.6
2. Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, Cua DJ, Littman DR. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 2006;126(6):1121-1133
3. Amadi-Obi A, Yu CR, Liu X, Mahdi RM, Clarke GL, Nussenblatt RB, Gery I, Lee YS, Egwuagu CE. TH17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1. Nat Med 2007; 13(6):711-718
4. Chi W, Yang P, Li B, Wu C, Jin H, Zhu X, Chen L, Zhou H, Huang X, Kijlstra A. IL-23 promotes CD4+ T cells to produce IL-17 in Vogt-Koyanagi-Harada disease. J Allergy Clin Immunol 2007;119(5):1218-1224
5. Luger D, Silver PB, Tang J, Cua D, Chen Z, Iwakura Y, Bowman EP, Sgambellone NM, Chan CC, Caspi RR. Either a Th17 or a Th1 effector response can drive autoimmunity:conditions of disease induction affect dominant effector category. J Exp Med 2008;205(4):799-810
6. Damsker JM, Hansen AM, Caspi RR. Th1 and Th17 cells:adversaries and collaborators. Ann. N Y Acad Sci 2010;1183:211-221
7. Horai R, Caspi RR. Cytokines in autoimmune uveitis. J Interferon Cytokine Res 2011;31(10):733-744
8. Kim SJ, Zhang M, Vistica BP, Chan CC, Shen DF, Wawrousek EF, Gery I. Induction of ocular inflammation by T-helper lymphocytes type 2. Invest Ophthalmol Vis Sci 2002;43(3):758-765
9. Ke Y, Jiang G, Sun D, Kaplan HJ, Shao H. Ocular regulatory T cells distinguish monophasic from recurrent autoimmune uveitis. Invest Ophthalmol Vis Sci 2008;49(9):3999-4007
10. Sun M, Yang P, Du L, Zhou H, Ren X, Kijlstra A. Contribution of CD4+CD25+ T cells to the regression phase of experimental autoimmune uveoretinitis. Invest Ophthalmol Vis Sci 2010;51(1):383-389
11. Zhang L, Ma J, Takeuchi M, Usui Y, Hattori T, Okunuki Y, Yamakawa N, Kezuka T, Kuroda M, Goto H. Suppression of experimental autoimmune uveoretinitis by inducing differentiation of regulatory T cells via activation of arylhydrocarbon receptor. Invest Ophthalmol Vis Sci 2010;51(4):2109-2017
12. Sehgal SN, Baker H, Vezina C. Rapamycin, a new antifungal antibiotic. II. Fermentation, isolation and characterization. J Antibiot (Tokyo) 1975;28(10):727-732
13. Morris RE, Wu J, Shorthouse R. A study of the contrasting effects of cyclosporine, FK 506, and rapamycin on the suppression of allograft rejection. Transplant Proc 1990;22(4):1638-1641
14. Augustine JJ, Bodziak KA, Hricik DE. Use of sirolimus in solid organ transplantation. Drugs 2007; 67(3):369-391
15. Roberge FG, Xu D, Chan CC, de Smet MD, Nussenblatt RB, Chen H. Treatment of autoimmune uveoretinitis in the rat with rapamycin, an inhibitor of lymphocyte growth factor signal transduction. Curr Eye Res 1993; 12(2):197-203
16. Roberge FG, Kozhich A, Chan CC, Martin DF, Nussenblatt RB, De Smet MD. Inhibition of cellular transfer of experimental autoimmune uveoretinitis by Rapamycin. Ocul Immunol Inflamm 1993;1(3):269-273
17. Shanmuganathan VA, Casely EM, Raj D, Powell RJ, Joseph A, Amoaku WM, Dua HS. The efficacy of sirolimus in the treatment of patients with refractory uveitis. Br J Ophthalmol 2005;89(6):666-669
18. Nussenblatt RB, Coleman H, Jirawuthiworavong G, Davuluri G, Potapova N, Dahr SS, Ragheb JA, Levy-Clarke G. The treatment of multifocal choroiditis associated choroidal neovascularization with sirolimus (rapamycin). Acta Ophthalmol Scand 2007;85(2):230-231
19. Phillips BN, Wroblewski KJ. A retrospective review of oral low-dose sirolimus (rapamycin) for the treatment of active uveitis. J Ophthalmic Inflamm Infect 2010;1(1):29-34
20. Mudumba S, Bezwada P, Takanaga H, Hosoi K, Tsuboi T, Ueda K, Kawazu K, Ali Y, Naor J. Tolerability and Pharmacokinetics of Intravitreal Sirolimus. J Ocul Pharmacol Ther 2012;28(5):507-514
21. Zhang X, Ren X, Li G, Jiao C, Zhang L, Zhao S, Wang J, Han ZC, Li X. Mesenchymal stem cells ameliorate experimental autoimmune uveoretinitis by comprehensive modulation of systemic autoimmunity. Invest Ophthalmol Vis Sci 2011;52(6):3143-3152
22. Servat JJ, Mears KA, Black EH, Huang JJ. Biological agents for the treatment of uveitis. Expert Opin Biol Ther 2012;12(3):311-328
23. Martin DF, DeBarge LR, Nussenblatt RB, Chan CC, Roberge FG. Synergistic effect of rapamycin and cyclosporin A in the treatment of experimental autoimmune uveoretinitis. J Immunol 1995;154(2):922-927
24. Roberge FG, Martin DF, Xu D, Chen H, Chan CC. Synergism between corticosteroids and Rapamycin for the treatment of intraocular inflammation. Ocul Immunol Inflamm. 1995;3(3):195-202
25. Ikeda E, Hikita N, Eto K, Mochizuki M. Tacrolimus-rapamycin combination therapy for experimental autoimmune uveoretinitis. Jpn J Ophthalmol1997; 41(6):396-402
26. Zhang Z, Wu X, Duan J, Hinrichs D, Wegmann K, Zhang GL, Hall M, Rosenbaum JT. Low dose rapamycin exacerbates autoimmune experimental uveitis. PLoS One 2012;7(5):e36589
27. Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, Weiner HL, Kuchroo VK. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 2006; 441(7090):235-238
28. Ferraro A, Socci C, Stabilini A, Valle A, Monti P, Piemonti L, Nano R, Olek S, Maffi P, Scavini M, Secchi A, Staudacher C, Bonifacio E, Battaglia M. Expansion of Th17 cells and functional defects in T regulatory cells are key features of the pancreatic lymph nodes in patients with type 1 diabetes. Diabetes 2011;60(11):2903-2913
29. Niu Q, Cai B, Huang ZC, Shi YY, Wang LL. Disturbed Th17/Treg balance in patients with rheumatoid arthritis. Rheumatol Int 2012;32(9):2731-2736
30. Khoury SJ. Th17 and Treg balance in systemic sclerosis. Clin Immunol 2011;139(3):231-232
31. Zhou L, Lopes JE, Chong MM, Ivanov II, Min R, Victora GD, Shen Y, Du J, Rubtsov YP, Rudensky AY, Ziegler SF, Littman DR. TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function. Nature 2008;453(7192):236-240
32. Korn T, Mitsdoerffer M, Croxford AL, Awasthi A, Dardalhon VA, Galileos G, Vollmar P, Stritesky GL, Kaplan MH, Waisman A, Kuchroo VK, Oukka M. IL-6 controls Th17 immunity in vivo by inhibiting the conversion of conventional T cells into Foxp3+ regulatory T cells. Proc Natl Acad Sci U S A2008;105(47):18460-18465
33. Kopf H, de la Rosa GM, Howard OM, Chen X. Rapamycin inhibits differentiation of Th17 cells and promotes generation of FoxP3+ T regulatory cells. Int Immunopharmacol 2007;7(13):1819-1824
34. Lee K, Gudapati P, Dragovic S, Spencer C, Joyce S, Killeen N, Magnuson MA, Boothby M. Mammalian target of rapamycin protein complex 2 regulates differentiation of Th1 and Th2 cell subsets via distinct signaling pathways. Immunity 2010;32(6):743-753
35. Chan S. Targeting the mammalian target of rapamycin (mTOR):a new approach to treating cancer. Br J Cancer 2004;91(8):1420-1424
36. Donia M, Mangano K, Amoroso A, Mazzarino MC, Imbesi R, Castrogiovanni P, Coco M, Meroni P, Nicoletti F. Treatment with rapamycin ameliorates clinical and histological signs of protracted relapsing experimental allergic encephalomyelitis in Dark Agouti rats and induces expansion of peripheral CD4+CD25+Foxp3+ regulatory T cells. J Autoimmun 2009;33(2):135-140
37. Esposito M, Ruffini F, Bellone M, Gagliani N, Battaglia M, Martino G, Furlan R. Rapamycin inhibits relapsing experimental autoimmune encephalomyelitis by both effector and regulatory T cells modulation. J Neuroimmunol. 2010;220(1-2):52-63
38. Yang K, Wen J, Liu X, Kijlstra A, Chen L, Chi W, Zhou H, Huang X, Yang P. Inhibitory effect of rapamycin and dexamethasone on production of IL-17 and IFN-gamma in Vogt-Koyanagi-Harada patients. Br J Ophthalmol 2009;93(2):249-253