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http://dx.doi.org/10.14405/kjvr.2014.54.4.209

Increased expression of galectin-9 in experimental autoimmune encephalomyelitis  

Cho, Jinhee (Department of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University)
Bing, So Jin (Department of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University)
Kim, Areum (Department of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University)
Yu, Hak Sun (Department of Parasitology, School of Medicine, Pusan National University)
Lim, Yoon-Kyu (Department of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University)
Shin, Taekyun (Department of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University)
Choi, Jonghee (Department of Convergence Medical Science and Brain Korea 21 Plus Program, College of Oriental Medicine, Kyunghee University)
Jee, Youngheun (Department of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University)
Publication Information
Korean Journal of Veterinary Research / v.54, no.4, 2014 , pp. 209-218 More about this Journal
Abstract
Experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS), reflects pathophysiologic steps in MS such as the influence of T cells and antibodies reactive to the myelin sheath, and the cytotoxic effect of cytokines. Galectin-9 (Gal-9) is a member of animal lectins that plays an essential role in various biological functions. The expression of Gal-9 is significantly enhanced in MS lesions; however, its role in autoimmune disease has not been fully elucidated. To identify the role of Gal-9 in EAE, we measured changes in mRNA and protein expression of Gal-9 as EAE progressed. Expression increased with disease progression, with a sharp rise occurring at its peak. Gal-9 immunoreactivity was mainly expressed in astrocytes and microglia of the central nervous system (CNS) and macrophages of spleen. Flow cytometric analysis revealed that $Gal-9^+CD11b^+$ cells were dramatically increased in the spleen at the peak of disease. Increased expression of tumor necrosis factor (TNF)-R1 and p-Jun N-terminal kinase (JNK) was observed in the CNS of EAE mice, suggesting that TNF-R1 and p-JNK might be key regulators contributing to the expression of Gal-9 during EAE. These results suggest that identification of the relationship between Gal-9 and EAE progression is critical for better understanding Gal-9 biology in autoimmune disease.
Keywords
central nervous system; experimental autoimmune encephalomyelitis; Galectin-9;
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1 Seki M, Oomizu S, Sakata KM, Sakata A, Arikawa T, Watanabe K, Ito K, Takeshita K, Niki T, Saita N, Nishi N, Yamauchi A, Katoh S, Matsukawa A, kuchroo V, Hirashima M. Galectin-9 suppresses the generation of Th17, promotes the induction of regulatory T cells, and regulates experimental autoimmune arthritis. Clin Immunol 2008, 127, 78-88.   DOI   ScienceOn
2 Suvannavejh GC, Lee HO, Padilla J, Dal canto MC, Barrett TA, Miller SD. Divergent roles for p55 and p75 tumor necrosis factor receptors in the pathogenesis of $MOG_{35-55}$-induced experimental autoimmune encephalomyelitis. Cell Immunol 2000, 205, 24-33.   DOI
3 Seki M, Sakata KM, Oomizu S, Arikawa T, Sakata A, Ueno M, Nobumoto A, Niki T, Saita N, Ito K, Dai SY, Katoh S, Nishi N, Tsukano M, Ishikawa K, Yamauchi A, Kuchroo V, Hirashima M. Beneficial effect of galectin 9 on rheumatoid arthritis by induction of apoptosis of synovial fibroblasts. Arthritis Rheum 2007, 56, 3968-3976.   DOI
4 Stancic M, van Horssen J, Thijssen VL, Gabius HJ, van der Valk P, Hoekstra D, Baron W. Increased expression of distinct galectins in multiple sclerosis lesions. Neuropathol Appl Neurobiol 2011, 37, 654-671.   DOI
5 Steelman AJ, Smith R 3rd, Welsh CJ, Li J. Galectin-9 is up-regulated in astrocytes by tumor necrosis factor and promotes encephalitogenic T-cell apoptosis. J Biol Chem 2013, 288, 23776-23787.   DOI
6 Teitelbaum D, Aharoni R, Sela M, Arnon R. Cross-reactions and specificities of monoclonal antibodies against myelin basic protein and against the synthetic copolymer 1. Proc Natl Acad Sci USA 1991, 88, 9528-9532.   DOI
7 Troncoso MF, Elola MT, Croci DO, Rabinovich GA. Integrating structure and function of 'tandem-repeat' galectins. Front Biosci (Schol Ed) 2012, 4, 864-887.
8 Tsuchiyama Y, Wada J, Zhang H, Morita Y, Hiraqushi K, Hida K, Shikata K, Yamamura M, Kanwar YS, Makino H. Efficacy of galectins in the amelioration of nephrotoxic serum nephritis in Wistar Kyoto rats. Kidney Int 2000, 58, 1941-1952.   DOI
9 Wang F, Wan L, Zhang C, Zheng X, Li J, Chen ZK. Tim-3-galectin-9 pathway involves the suppression induced by $CD4^+CD25^+$ regulatory T cells. Immunobiology 2009, 214, 342-349.   DOI
10 Weber F, Rieckmann P. Pathogenesis and therapy of multiple sclerosis. The role of cytokines. Nervenarzt 1995, 66, 150-155.
11 Yang RY, Rabinovich GA, Liu FT. Galectins: structure, function and therapeutic potential. Expert Rev Mol Med 2008, 10, e17.   DOI
12 Zhu C, Anderson AC, Schubart A, Xiong H, Imitola J, Khoury SJ, Zheng XX, Strom TB, Kuchroo VK. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol 2005, 6, 1245-1252.   DOI   ScienceOn
13 Eugster HP, Frei K, Bachmann R, Bluethmann H, Lassmann H, Fontana A. Severity of symptoms and demyelination in MOG-induced EAE depends on TNFR1. Eur J Immunol 1999, 29, 626-632.   DOI
14 Al-Omaishi J, Bashir R, Gendelman HE. The cellular immunology of multiple sclerosis. J Leukoc Biol 1999, 65, 444-452.   DOI
15 Arima Y, Harada M, Kamimura D, Park JH, Kawano F, Yull FE, Kawamoto T, Iwakura Y, Betz UA, Marquez G, Blackwell TS, Ohira Y, Hirano T, Murakami M. Regional neural activation defines a gateway for autoreactive T cells to cross the blood-brain barrier. Cell 2012, 148, 447-457.   DOI
16 Cannella B, Gao YL, Brosnan C, Raine CS. IL-10 fails to abrogate experimental autoimmune encephalomyelitis. J Neurosci Res 1996, 45, 735-746.   DOI
17 Carneiro-Sampaio M, Coutinho A. Tolerance and autoimmunity: lessons at the bedside of primary immunodeficiencies. Adv Immunol 2007, 95, 51-82.   DOI
18 Leitner J, Rieger A, Pickl WF, Zlabinger G, Grabmeier-Pfistershammer K, Steinberger P. Tim-3 does not act as a receptor for galectin-9. PLoS Pathog 2013, 9, e1003253.   DOI
19 Goverman J. Autoimmune T cell responses in the central nervous system. Nat Rev Immunol 2009, 9, 393-407.   DOI
20 Lim SY, Constantinescu CS. TNF-${\alpha}$: a paradigm of paradox and complexity in multiple sclerosis and its animal models. Open Autoimmun J 2010, 2, 160-170.   DOI
21 Liu FT, Patterson RJ, Wang JL. Intracellular functions of galectins. Biochim Biophys Acta 2002, 1572, 263-273.   DOI   ScienceOn
22 Liu FT, Rabinovich GA. Galectins: regulators of acute and chronic inflammation. Ann N Y Acad Sci 2010, 1183, 158-182.   DOI
23 Liu J, Miwa T, Hilliard B, Chen Y, Lambris JD, Wells AD, Song WC. The complement inhibitory protein DAF (CD55) suppresses T cell immunity in vivo. J Exp Med 2005, 201, 567-577.   DOI
24 Martin R, McFarland HF, McFarlin DE. Immunological aspects of demyelinating diseases. Annu Rev Immunol 1992, 10, 153-187.   DOI   ScienceOn
25 Pulendran B, van Driel R, Nossal GJV. Immunological tolerance in germinal centres. Immunol Today 1997, 18, 27-32.
26 Oomizu S, Arikawa T, Niki T, Kadowaki T, Ueno M, Nishi N, Yamauchi A, Hattori T, Masaki T, Hirashima M. Cell surface galectin-9 expressing Th cells regulate Th17 and $Foxp3^+$ Treg development by galectin-9 secretion. PLoS One 2012, 7, e48574.   DOI
27 Raine CS, Traugott U. Experimental autoimmune demyelination. Chronic relapsing models and their therapeutic implication for multiple sclerosis. Ann N Y Acad Sci 1984, 436, 33-51.   DOI   ScienceOn
28 Oomizu S, Arikawa T, Niki T, Kadowaki T, Ueno M, Nishi N, Yamauchi A, Hirashima M. Galectin-9 suppresses Th17 cell development in an IL-2-dependent but Tim-3-independent manner. Clin Immunol 2012, 143, 51-58.   DOI
29 Rabinovich GA, Liu FT, Hirashima M, Anderson A. An emerging role for galectins in tuning the immune response: lessons from experimental models of inflammatory disease, autoimmunity and cancer. Scand J Immunol 2007, 66, 143-158.   DOI   ScienceOn
30 Ransohoff RM, Engelhardt B. The anatomical and cellular basis of immune surveillance in the central nervous system. Nat Rev Immunol 2012, 12, 623-635.   DOI
31 Romero MD, Muino JC, Bianco GA, Ferrero M, Juarez CP, Luna JD, Rabinovich GA. Circulating anti-galectin-1 antibodies are associated with the severity of ocular disease in autoimmune and infectious uveitis. Invest Ophthalmol Vis Sci 2006, 47, 1550-1556.   DOI
32 Rott O, Fleischer B, Cash E. Interleukin-10 prevents experimental allergic encephalomyelitis in rats. Eur J Immunol 1994, 24, 1434-1440.   DOI
33 Kuruvilla AP, Shah R, Hochwald GM, Liggitt HD, Palladino MA, Thorbecke GJ. Protective effect of transforming growth factor ${\beta}_1$ on experimental autoimmune disease in mice. Proc Natl Acad Sci U S A 1991, 88, 2918-2921.   DOI   ScienceOn