EXPERIMENTAL IMMUNOLOGY
Mature dendritic cells cause Th17/Treg imbalance by secreting TGF-β1 and IL-6 in the pathogenesis of experimental autoimmune encephalomyelitis
Submission date: 2015-07-06
Final revision date: 2015-10-28
Acceptance date: 2015-11-26
Publication date: 2016-07-15
Cent Eur J Immunol 2016;41(2):143-152
KEYWORDS
ABSTRACT
Multiple sclerosis (MS) is generally acknowledged to be an autoimmune disease, but its etiology remains unknown. The most intensively studied animal model of MS is experimental autoimmune encephalomyelitis (EAE). Dendritic cells (DCs), the professional antigen presenting cells (APCs), have gained increasing attention because they connect innate and adaptive immunity. The aim of this study was to determine the role of mature DCs in the pathogenesis of EAE. It was found that the number of mature DCs in the EAE spleen increased compared to the control group (p < 0.05). And there was an imbalance between Th17 (effector) and Treg (regulatory) in EAE. The data showed that mature DCs can regulate the differentiation of Th17 and Treg in EAE. In addition, there was a significant difference in secretion of TGF-β1 and IL-6 between mature DCs from mice with EAE and controls. The present data suggest that mature DCs cause an imbalance between Th17 and Treg by secreting TGF-β1 and IL-6 in the pathogenesis of EAE disease. Thus, targeting DC may be an effective strategy for treating MS.
REFERENCES (36)
1.
Confavreux C, Vukusic S (2006): Accumulation of irreversible disability in multiple sclerosis: from epidemiology to treatment. Clin Neurol Neurosurg 108: 327-32.
2.
Chun J, Hartung HP (2010): Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis. Clin Neuropharmacol 33: 91-101.
3.
Turley DM, Miller SD (2007): Peripheral tolerance induction using ethylenecarbodiimide-fixed APCs uses both direct and indirect mechanisms of antigen presentation for prevention of experimental autoimmune encephalomyelitis. J Immunol 178: 2212-2220.
4.
Fletcher JM, Lalor SJ, Sweeney CM, et al. (2010): T cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Clin Exp Immunol 162: 1-11.
5.
Seger J, Zorzella-Pezavento SF, Pelizon AC, et al. (2010): Decreased production of TNF-αlpha by lymph node cells indicates experimental autoimmune encephalomyelitis remission in Lewis rats. Mem Inst Oswaldo Cruz 105: 263-268.
6.
Zorzella-Pezavento SF, Chiuso-Minicucci F, Franca TG, et al. (2010): Immunization with pVAXhsp65 decreases inflammation and modulates immune response in experimental encephalomyelitis. Neuroimmunomodulation 17: 287-297.
7.
Pollinger B (2012): IL-17 producing T cells in mouse models of multiple sclerosis and rheumatoid arthritis. J Mol Med (Berl) 90: 613-624.
8.
Fernando V, Omura S, Sato F, et al. (2014): Regulation of an autoimmune model for multiple sclerosis in Th2-biased GATA3 transgenic mice. Int J Mol Sci 15: 1700-1718.
9.
Petermann F, Korn T (2011): Cytokines and effector T cell subsets causing autoimmune CNS disease. FEBS Lett 585: 3747-3757.
10.
Adema GJ (2009): Dendritic cells from bench to bedside and back. Immunol Lett 122: 128-130.
11.
Li M, Li W, Wen S, et al. (2013): Effects of ceftriaxone-induced intestinal dysbacteriosis on dendritic cells of small intestine in mice. Microbiol Immunol 57: 561-568.
12.
Ohnmacht C, Pullner A, King SB, et al. (2009): Constitutive ablation of dendritic cells breaks self-tolerance of CD4 T cells and results in spontaneous fatal autoimmunity. J Exp Med 206: 549-559.
13.
Rutella S, Danese S, Leone G (2006): Tolerogenic dendritic cells: cytokine modulation comes of age. Blood 108: 1435-1440.
14.
Louis CU, Brenner MK (2009): Cellular immunotherapy for neuroblastoma: a review of current vaccine and adoptive T cell therapeutics. Curr Pharm Des 15: 424-429.
15.
Griffiths KL, O’Neill HC (2008): Dendritic cells as immune regulators: the mouse model. J Cell Mol Med 12: 1909-1914.
16.
Johnson AJ, Nelson MH, Bird MD, et al. (2010): Herpes simplex virus (HSV)-specific T cells activated in the absence of IFN-gamma express alternative effector functions but are not protective against genital HSV-2 infection. J Reprod Immunol 84: 8-15.
17.
Stromnes IM, Goverman JM (2006): Active induction of experimental allergic encephalomyelitis. Nat Protoc 1: 1810-1819.
18.
Watanabe T, Yamashita K, Fujikawa S, et al. (2012): Involvement of activation of toll-like receptors and nucleotide-binding oligomerization domain-like receptors in enhanced IgG4 responses in autoimmune pancreatitis. Arthritis Rheum 64: 914-924.
19.
Choi JH, Do Y, Cheong C, et al. (2009): Identification of antigen-presenting dendritic cells in mouse aorta and cardiac valves. J Exp Med 206: 497-505.
20.
Shachar I, Karin N (2013): The dual roles of inflammatory cytokines and chemokines in the regulation of autoimmune diseases and their clinical implications. J Leukoc Biol 93: 51-61.
21.
Petrausch U, Jensen SM, Twitty C, et al. (2009): Disruption of TGF-beta signaling prevents the generation of tumor-sensitized regulatory T cells and facilitates therapeutic antitumor immunity. J Immunol 183: 3682-3689.
22.
Banchereau J, Briere F, Caux C, et al. (2000): Immunobiology of dendritic cells. Annu Rev Immunol 18: 767-811.
23.
Banchereau J, Steinman RM (1998): Dendritic cells and the control of immunity. Nature 392: 245-252.
24.
Liu K, Victora GD, Schwickert TA, et al. (2009): In vivo analysis of dendritic cell development and homeostasis. Science 324: 392-397.
25.
Liu K, Nussenzweig MC (2010): Origin and development of dendritic cells. Immunol Rev 234: 45-54.
26.
Yu X, Wang C, Luo J, et al. (2013): Combination with methotrexate and cyclophosphamide attenuated maturation of dendritic cells: inducing Treg skewing and Th17 suppression in vivo. Clin Dev Immunol 2013: 238035.
27.
Gross CC, Wiendl H (2013): Dendritic cell vaccination in autoimmune disease. Curr Opin Rheumatol 25: 268-274.
28.
Batoulis H, Recks MS, Addicks K, Kuerten S (2011): Experimental autoimmune encephalomyelitis – achievements and prospective advances. APMIS 119: 819-830.
29.
Zheng Q, Yang T, Fang L, et al. (2015): Effects of Bu Shen Yi Sui Capsule on Th17/Treg cytokines in C57BL/6 mice with experimental autoimmune encephalomyelitis. BMC Complement Altern Med 15: 60.
30.
Bettelli E, Carrier Y, Gao W, et al. (2006): Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441: 235-238.
31.
Awasthi A, Murugaiyan G, Kuchroo VK (2008): Interplay between effector Th17 and regulatory T cells. J Clin Immunol 28: 660-670.
32.
Acharya M, Mukhopadhyay S, Paidassi H, et al. (2010): alphav Integrin expression by DCs is required for Th17 cell differentiation and development of experimental autoimmune encephalomyelitis in mice. J Clin Invest 120: 4445-4452.
33.
Karpus WJ, Swanborg RH (1991): Protection against experimental autoimmune encephalomyelitis requires both CD4+ T suppressor cells and myelin basic protein-primed B cells. J Neuroimmunol 33: 173-177.
34.
Mangan PR, Harrington LE, O’Quinn DB, et al. (2006): Transforming growth factor-beta induces development of the T(H)17 lineage. Nature 441: 231-234.
35.
Sen D (2010) Selective and site-specific mobilization of dermal dendritic cells and Langerhans cells by Th1- and Th2- polarizing adjuvants.Proc Natl Acad Sci 107: 8334-8339.
36.
Oukka M (2007): Interplay between pathogenic Th17 and regulatory T cells. Ann Rheum Dis 66 Suppl 3: iii87-90.
Share
RELATED ARTICLE
| eISSN: | 1644-4124 |
| ISSN: | 1426-3912 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
