Exosomes derived from atorvastatin-modified bone marrow dendritic cells ameliorate experimental autoimmune myasthenia gravis by up-regulated levels of IDO/Treg and partly dependent on FasL/Fas pathway

详细信息    查看全文

• 作者：Xiao-Li Li ; Heng Li ; Min Zhang ; Hua Xu ; Long-Tao Yue…
• 关键词：Atorvastatin ; Exosomes ; Experimental autoimmune myasthenia gravis ; IDO ; FasL
• 刊名：Journal of Neuroinflammation
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：13
• 期：1
• 全文大小：2,053 KB
• 参考文献：1.Vincent A, Palace J, Hilton-Jones D. Myasthenia gravis. Lancet. 2001;357:2122–8.PubMed CrossRef
  2.Elson CJ, Barker RN. Helper T cells in antibody-mediated, organ-specific autoimmunity. Curr Opin Immunol. 2000;12:664–9.PubMed CrossRef
  3.Baggi F, Annoni A, Ubiali F, Milani M, Longhi R, Scaioli W, et al. Breakdown of tolerance to a self-peptide of acetylcholine receptor alpha-subunit induces experimental myasthenia gravis in rats. J Immunol. 2004;172:2697–703.PubMed CrossRef
  4.Angelini C, Martignago S, Bisciglia M. New treatments for myasthenia: a focus on antisense oligonucleotides. Drug Des Devel Ther. 2013;7:13–7.PubMed PubMedCentral CrossRef
  5.Rowin J. Etanercept treatment in myasthenia gravis. Ann N Y Acad Sci. 2008;1132:300–4.PubMed CrossRef
  6.Kim JY, Park KD, Richman DP. Treatment of myasthenia gravis based on its immunopathogenesis. J Clin Neurol. 2011;7:173–83.PubMed PubMedCentral CrossRef
  7.Xiao BG, Duan RS, Link H, Huang YM. Induction of peripheral tolerance to experimental autoimmune myasthenia gravis by acetylcholine receptor-pulsed dendritic cells. Cell Immunol. 2003;223:63–9.PubMed CrossRef
  8.Duan RS, Adikari SB, Huang YM, Link H, Xiao BG. Protective potential of experimental autoimmune myasthenia gravis in Lewis rats by IL-10-modified dendritic cells. Neurobiol Dis. 2004;16:461–7.PubMed CrossRef
  9.Duan RS, Link H, Xiao BG. Long-term effects of IFN-gamma, IL-10, and TGF-beta-modulated dendritic cells on immune response in Lewis rats. J Clin Immunol. 2005;25:50–6.PubMed CrossRef
  10.Yang H, Zhang Y, Wu M, Li J, Zhou W, Li G, et al. Suppression of ongoing experimental autoimmune myasthenia gravis by transfer of RelB-silenced bone marrow dendritic cells is associated with a change from a T helper Th17/Th1 to a Th2 and FoxP3+ regulatory T-cell profile. Inflamm Res. 2010;59:197–205.PubMed CrossRef
  11.Yarilin D, Duan R, Huang YM, Xiao BG. Dendritic cells exposed in vitro to TGF-beta1 ameliorate experimental autoimmune myasthenia gravis. Clin Exp Immunol. 2002;127:214–9.PubMed PubMedCentral CrossRef
  12.Mehrbod P, Hair-Bejo M, Tengku Ibrahim TA, Omar AR, El Zowalaty M, Ajdari Z, et al. Simvastatin modulates cellular components in influenza A virus-infected cells. Int J Mol Med. 2014;34:61–73.PubMed PubMedCentral
  13.Agarwal P, Rashighi M, Essien KI, Richmond JM, Randall L, Pazoki-Toroudi H, et al. Simvastatin prevents and reverses depigmentation in a mouse model of vitiligo. J Invest Dermatol. 2015;135:1080–8.PubMed PubMedCentral CrossRef
  14.Tsakiri A, Tsiantoulas D, Frederiksen J, Svane IM. Increased immunopotency of monocyte derived dendritic cells from patients with optic neuritis is inhibited in vitro by simvastatin. Exp Neurol. 2010;221:320–8.PubMed CrossRef
  15.Li XL, Liu Y, Cao LL, Li H, Yue LT, Wang S, et al. Atorvastatin-modified dendritic cells in vitro ameliorate experimental autoimmune myasthenia gravis by up-regulated Treg cells and shifted Th1/Th17 to Th2 cytokines. Mol Cell Neurosci. 2013;56C:85–95.CrossRef
  16.Thery C, Regnault A, Garin J, Wolfers J, Zitvogel L, Ricciardi-Castagnoli P, et al. Molecular characterization of dendritic cell-derived exosomes. Selective accumulation of the heat shock protein hsc73. J Cell Biol. 1999;147:599–610.PubMed PubMedCentral CrossRef
  17.Zhang H, Xie Y, Li W, Chibbar R, Xiong S, Xiang J. CD4(+) T cell-released exosomes inhibit CD8(+) cytotoxic T-lymphocyte responses and antitumor immunity. Cell Mol Immunol. 2011;8:23–30.PubMed PubMedCentral CrossRef
  18.Yang C, Kim SH, Bianco NR, Robbins PD. Tumor-derived exosomes confer antigen-specific immunosuppression in a murine delayed-type hypersensitivity model. PLoS One. 2011;6:e22517.PubMed PubMedCentral CrossRef
  19.Johansson SM, Admyre C, Scheynius A, Gabrielsson S. Different types of in vitro generated human monocyte-derived dendritic cells release exosomes with distinct phenotypes. Immunology. 2008;123:491–9.PubMed PubMedCentral CrossRef
  20.Hammond C, Denzin LK, Pan M, Griffith JM, Geuze HJ, Cresswell P. The tetraspan protein CD82 is a resident of MHC class II compartments where it associates with HLA-DR, -DM, and -DO molecules. J Immunol. 1998;161:3282–91.PubMed
  21.Lamparski HG, Metha-Damani A, Yao JY, Patel S, Hsu DH, Ruegg C, et al. Production and characterization of clinical grade exosomes derived from dendritic cells. J Immunol Methods. 2002;270:211–26.PubMed CrossRef
  22.Zitvogel L, Regnault A, Lozier A, Wolfers J, Flament C, Tenza D, et al. Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nat Med. 1998;4:594–600.PubMed CrossRef
  23.Kim SH, Bianco N, Menon R, Lechman ER, Shufesky WJ, Morelli AE, et al. Exosomes derived from genetically modified DC expressing FasL are anti-inflammatory and immunosuppressive. Mol Ther. 2006;13:289–300.PubMed CrossRef
  24.Andre F, Andersen M, Wolfers J, Lozier A, Raposo G, Serra V, et al. Exosomes in cancer immunotherapy: preclinical data. Adv Exp Med Biol. 2001;495:349–54.PubMed CrossRef
  25.Morse MA, Garst J, Osada T, Khan S, Hobeika A, Clay TM, et al. A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer. J Transl Med. 2005;3:9.PubMed PubMedCentral CrossRef
  26.Bu N, Wu HQ, Zhang GL, Zhan SQ, Zhang R, Fan QY, et al. Immature dendritic cell exosomes suppress experimental autoimmune myasthenia gravis. J Neuroimmunol. 2015;285:71–5.PubMed CrossRef
  27.Yang X, Meng S, Jiang H, Zhu C, Wu W. Exosomes derived from immature bone marrow dendritic cells induce tolerogenicity of intestinal transplantation in rats. J Surg Res. 2011;171:826–32.PubMed CrossRef
  28.Sarkhosh K, Tredget EE, Karami A, Uludag H, Iwashina T, Kilani RT, et al. Immune cell proliferation is suppressed by the interferon-gamma-induced indoleamine 2,3-dioxygenase expression of fibroblasts populated in collagen gel (FPCG). J Cell Biochem. 2003;90:206–17.PubMed CrossRef
  29.Fallarino F, Grohmann U, You S, McGrath BC, Cavener DR, Vacca C, et al. The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells. J Immunol. 2006;176:6752–61.PubMed CrossRef
  30.Funeshima N, Fujino M, Kitazawa Y, Hara Y, Hayakawa K, Okuyama T, et al. Inhibition of allogeneic T-cell responses by dendritic cells expressing transduced indoleamine 2,3-dioxygenase. J Gene Med. 2005;7:565–75.PubMed CrossRef
  31.Jurgens B, Hainz U, Fuchs D, Felzmann T, Heitger A. Interferon-gamma-triggered indoleamine 2,3-dioxygenase competence in human monocyte-derived dendritic cells induces regulatory activity in allogeneic T cells. Blood. 2009;114:3235–43.PubMed CrossRef
  32.Xu J, Yao N, Li YD. T-cell proliferation is inhibited by the induction of indoleamine 2,3-dioxygenase in spleen-derived dendritic cells in rat. Chin Med J (Engl). 2011;124:3154–8.
  33.Bianco NR, Kim SH, Ruffner MA, Robbins PD. Therapeutic effect of exosomes from indoleamine 2,3-dioxygenase-positive dendritic cells in collagen-induced arthritis and delayed-type hypersensitivity disease models. Arthritis Rheum. 2009;60:380–9.PubMed PubMedCentral CrossRef
  34.Raposo G, Nijman HW, Stoorvogel W, Liejendekker R, Harding CV, Melief CJ, et al. B lymphocytes secrete antigen-presenting vesicles. J Exp Med. 1996;183:1161–72.PubMed CrossRef
  35.Duchmann R, Schmitt E, Knolle P, Buschenfelde KH M z, Neurath M. Tolerance towards resident intestinal flora in mice is abrogated in experimental colitis and restored by treatment with interleukin-10 or antibodies to interleukin-12. Eur J Immunol. 1996;26:934–8.PubMed CrossRef
  36.Kim SH, Bianco NR, Shufesky WJ, Morelli AE, Robbins PD. Effective treatment of inflammatory disease models with exosomes derived from dendritic cells genetically modified to express IL-4. J Immunol. 2007;179:2242–9.PubMed CrossRef
  37.Denzer K, van Eijk M, Kleijmeer MJ, Jakobson E, de Groot C, Geuze HJ. Follicular dendritic cells carry MHC class II-expressing microvesicles at their surface. J Immunol. 2000;165:1259–65.PubMed CrossRef
  38.Thery C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol. 2009;9:581–93.PubMed CrossRef
  39.Montecalvo A, Shufesky WJ, Stolz DB, Sullivan MG, Wang Z, Divito SJ, et al. Exosomes as a short-range mechanism to spread alloantigen between dendritic cells during T cell allorecognition. J Immunol. 2008;180:3081–90.PubMed CrossRef
  40.Stoorvogel W, Kleijmeer MJ, Geuze HJ, Raposo G. The biogenesis and functions of exosomes. Traffic. 2002;3:321–30.PubMed CrossRef
  41.Thery C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2002;2:569–79.PubMed
  42.Lee YS, Kim SH, Cho JA, Kim CW. Introduction of the CIITA gene into tumor cells produces exosomes with enhanced anti-tumor effects. Exp Mol Med. 2011;43:281–90.PubMed PubMedCentral CrossRef
  43.Yang C, Ruffner MA, Kim SH, Robbins PD. Plasma-derived MHC class II+ exosomes from tumor-bearing mice suppress tumor antigen-specific immune responses. Eur J Immunol. 2012;42:1778–84.PubMed PubMedCentral CrossRef
  44.Segura E, Amigorena S, Thery C. Mature dendritic cells secrete exosomes with strong ability to induce antigen-specific effector immune responses. Blood Cells Mol Dis. 2005;35:89–93.PubMed CrossRef
  45.Mallegol J, Van Niel G, Lebreton C, Lepelletier Y, Candalh C, Dugave C, et al. T84-intestinal epithelial exosomes bear MHC class II/peptide complexes potentiating antigen presentation by dendritic cells. Gastroenterology. 2007;132:1866–76.PubMed CrossRef
  46.Buzas EI, Gyorgy B, Nagy G, Falus A, Gay S. Emerging role of extracellular vesicles in inflammatory diseases. Nat Rev Rheumatol. 2014;10(6):356–64.PubMed CrossRef
  47.Peng YP, Zhang JJ, Liang WB, Tu M, Lu ZP, Wei JS, et al. Elevation of MMP-9 and IDO induced by pancreatic cancer cells mediates natural killer cell dysfunction. BMC Cancer. 2014;14:738.PubMed PubMedCentral CrossRef
  48.Choi SW, Gatza E, Hou G, Sun Y, Whitfield J, Song Y, et al. Histone deacetylase inhibition regulates inflammation and enhances Tregs after allogeneic hematopoietic cell transplantation in humans. Blood. 2014;125(5):815–9.PubMed CrossRef
  49.Orsini H, Araujo LP, Maricato JT, Guereschi MG, Mariano M, Castilho BA, et al. GCN2 kinase plays an important role triggering the remission phase of experimental autoimmune encephalomyelitis (EAE) in mice. Brain Behav Immun. 2014;37:177–86.PubMed CrossRef
  50.Mellor AL, Munn DH. Physiologic control of the functional status of Foxp3+ regulatory T cells. J Immunol. 2011;186:4535–40.PubMed CrossRef
  51.Sharma MD, Hou DY, Baban B, Koni PA, He Y, Chandler PR, et al. Reprogrammed foxp3(+) regulatory T cells provide essential help to support cross-presentation and CD8(+) T cell priming in naive mice. Immunity. 2010;33:942–54.PubMed PubMedCentral CrossRef
  52.Matteoli G, Mazzini E, Iliev ID, Mileti E, Fallarino F, Puccetti P, et al. Gut CD103+ dendritic cells express indoleamine 2,3-dioxygenase which influences T regulatory/T effector cell balance and oral tolerance induction. Gut. 2010;59:595–604.PubMed CrossRef
  53.Park MJ, Park KS, Park HS, Cho ML, Hwang SY, Min SY, et al. A distinct tolerogenic subset of splenic IDO(+)CD11b(+) dendritic cells from orally tolerized mice is responsible for induction of systemic immune tolerance and suppression of collagen-induced arthritis. Cell Immunol. 2012;278:45–54.PubMed CrossRef
  54.De Maria R, Lenti L, Malisan F, d'Agostino F, Tomassini B, Zeuner A, et al. Requirement for GD3 ganglioside in CD95- and ceramide-induced apoptosis. Science. 1997;277:1652–5.PubMed CrossRef
  55.Abusamra AJ, Zhong Z, Zheng X, Li M, Ichim TE, Chin JL, et al. Tumor exosomes expressing Fas ligand mediate CD8+ T-cell apoptosis. Blood Cells Mol Dis. 2005;35:169–73.PubMed CrossRef
  56.Ichim TE, Zhong Z, Kaushal S, Zheng X, Ren X, Hao X, et al. Exosomes as a tumor immune escape mechanism: possible therapeutic implications. J Transl Med. 2008;6:37.PubMed PubMedCentral CrossRef
  57.Pellegrini M, Belz G, Bouillet P, Strasser A. Shutdown of an acute T cell immune response to viral infection is mediated by the proapoptotic Bcl-2 homology 3-only protein Bim. Proc Natl Acad Sci U S A. 2003;100:14175–80.PubMed PubMedCentral CrossRef
  58.Gale J, Danesh-Meyer HV. Statins can induce myasthenia gravis. J Clin Neurosci. 2014;21:195–7.PubMed CrossRef
  59.Oh SJ, Dhall R, Young A, Morgan MB, Lu L, Claussen GC. Statins may aggravate myasthenia gravis. Muscle Nerve. 2008;38:1101–7.PubMed PubMedCentral CrossRef
  60.Evans M, Rees A. The myotoxicity of statins. Curr Opin Lipidol. 2002;13:415–20.PubMed CrossRef
  61.Purvin V, Kawasaki A, Smith KH, Kesler A. Statin-associated myasthenia gravis: report of 4 cases and review of the literature. Medicine (Baltimore). 2006;85:82–5.PubMed CrossRef
  
• 作者单位：Xiao-Li Li (1)
  Heng Li (1)
  Min Zhang (1)
  Hua Xu (1) (2)
  Long-Tao Yue (3)
  Xin-Xin Zhang (4)
  Shan Wang (1)
  Cong-Cong Wang (1)
  Yan-Bin Li (1)
  Ying-Chun Dou (5)
  Rui-Sheng Duan (1)
  
  1. Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, 250014, People’s Republic of China
  2. Department of Neurology, The Central Hospital of Taian, Taian, 271000, People’s Republic of China
  3. Central Laboratory, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, 250014, People’s Republic of China
  4. School of Basic Medical Sciences, Jining Health School, Jining, 272000, People’s Republic of China
  5. College of Basic Medical Sciences, Shandong University of Traditional Chinese Medicine, Jinan, 250355, People’s Republic of China
  
• 刊物主题：Neurosciences; Neurology; Neurobiology; Immunology;
• 出版者：BioMed Central
• ISSN：1742-2094

文摘

Background Previously, we have demonstrated that spleen-derived dendritic cells (DCs) modified with atorvastatin suppressed immune responses of experimental autoimmune myasthenia gravis (EAMG). However, the effects of exosomes derived from atorvastatin-modified bone marrow DCs (BMDCs) (statin-Dex) on EAMG are still unknown.