免疫研究部 TOP
免疫研究部では、免疫細胞や炎症が神経障害を引き起こす仕組みを解明し、難治性神経疾患に
対する画期的な治療法を開発するため、日夜研究を続けています。特に中枢神経系の自己免疫
疾患である多発性硬化症(MS)や視神経脊髄炎(NMO)の基礎研究では、NATURE、NATURE
IMMUOL、PNASなどに論文を多数発表しています。レベルの高い基礎研究の成果を臨床応用に発展させる
実力を持ち、「神経免疫」の領域では日本を代表する研究拠点になっています。
最近では「医療スーパー特区」のプロジェクト研究を走らせ、独自に開発した新規治療薬の実用化に
力を入れている他、自己免疫や神経免疫の基礎研究も推進しています。
神経系の炎症・免疫応答の研究は神経難病の新しい治療法の開発に欠かせません。当研究部は海外の一流の研究室との交流も深め、新しい方法論を取り入れながら着実に歩み続けています。多発性硬化症の発症にNK細胞やNKT細胞が関係していることや、腸内細菌と自己免疫疾患、視神経脊髄炎とIL-6など、当研究室から世界に向けて発信して来た情報は数えきれません。この領域に関心のある大学院生、医師、研究者などの皆さんは、是非門を叩いてください。
当研究部はこの10年で数百編の論文を発表していますが、その中でコアになる代表的な
オリジナル業績(Publication highlights) は以下の通りです。
■ | Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica. Chihara N, Aranami T, Sato W, Miyazaki Y, Miyake S, Okamoto T, Ogawa M, Toda T, Yamamura, T. Proc Natl Acad Sci U S A 108:3701-3706, 2011 |
■ | Suppression of experimental autoimmune encephalomyelitis by Ghrelin. Theil MM, Miyake S, Mizuno M, Tomi C, Croxford JL, Hosoda H, Theil J, von Hoersten S, Yokote H, Chiba A, Lin Y, Oki S, Akamizu T, Kangawa K, Yamamura T. J Immunol 183: 2859-2866, 2009 |
■ | Synthetic retinoid AM80 inhibits Th17 cells and ameliorates EAE. Klemann C, Raveney BJE, Klemann AK, Ozawa T, von Hoersten S, Shudo K, Oki S, Yamamura T. Am J Pathol 174: 2234-2245, 2009 |
■ | NKT cell-dependent amelioration of a mouse model of multiple sclerosis by altering gut flora. Yokote H, Miyake S, Croxford JL, Oki S, Mizusawa H, Yamamura T. Am J Pathol 173: 1714-1723, 2008 |
■ | Orphan nuclear receptor NR4A2 expressed in T cells from multiple sclerosis mediates production of inflammatory cytokines. Doi Y, Oki S, Ozawa T, Hohjoh H, Miyake S, Yamamura T. Proc Natl Acad Sci U S A 105: 8381-8386, 2008 |
■ | Cutting Edge. Human Th17 cells are identified as bearing CCR2+CCR5-phenotype. Sato W, Aranami T, and Yamamura T. J Immunol 178:7525-7529, 2007 |
■ | Direct Suppression of CNS Autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells. Maresz K, Pryce G, Ponomarev ED, Marsicano G, Croxford JL, Shriver LP, Ledent C, Cheng X, Carrier E, Mann MK, Giovannoni G, Pertwee RG, Yamamura T, Buckley NE, Hillard CJ, Lutz B, Baker D, Dittel BN. Nat Med 13:492-497, 2007 |
■ | Selective COX-2 inhibitor celecoxib prevents experimental autoimmune encephalomyelitis through COX-2 independent pathway. Miyamoto K, Miyake S, Mizuno M, Oka N, Kusunoki S, and Yamamura T. Brain 129(Pt 8):1984-92, 2006 |
■ | Invariant Vα19i T cells regulate autoimmune inflammation. Croxford, J.L., S. Miyake, Y-Y. Huang, M. Shimamura, and T. Yamamura. Nat Immunol 7: 987 -994, 2006 |
■ | The involvement of Vα14 NKT cells in the pathogenesis of murine models of arthritis. Chiba A, Kaieda S, Oki S, Yamamura T, Miyake S. Arthr Rheumat 52: 1941-1948, 2005 |
■ | Microarray analysis identifies an aberrant expression of apoptosis and DNA damage-regulatory genes in multiple sclerosis. Satoh J-i, Nakanishi M, Koike F, Miyake S, Yamamoto T, Kawai M, Kikuchi S, Nomura K, Yokoyama K, Ota K, Kanda T, Fukazawa T, Yamamura T. Neurobiol Dis 18:537-550, 2005 |
■ | Modulation of CD1d-restrotced NKT cell responses by using N-acyl variants of α-galactosylceramides. Yu KOA, Im JS, Molano A, Dutronc Y, Illarionov PA, Forestier C, Fujiwara N, Arias I, Miyake S, Yamamura T, Chang Y-T, Besra GS, and S.A. Porcelli. Proc Natl Acad Sci U S A 102: 3383-3388, 2005 |
■ | More sympathy for autoimmunity with neuropeptide Y (NPY)? Bedoui S, Miyake S, Straub R, von Hoersten S, Yamamura T. Trends Immunol 25:508-512, 2004 |
■ | The regulatory role of natural killer cells in multiple sclerosis. Takahashi K, Aranami T, Endoh M, Miyake S, Yamamura T. Brain 127: 1917-1927, 2004 |
■ | The clinical implication and molecular mechanism of preferential IL-4 production by modified glycolipid-stimulated NKT cells. Oki S, Chiba A, Yamamura T, Miyake S. J Clin Invest 113: 1631-1640, 2004 |
■ | Accumulation of Vα7.2Jα33 invariant T cells in autoimmune inflammatory lesions of the nervous system. Illes Zs, Shimamura M, Newcombe J, Oka N, Yamamura T. Int Immunol 16: 223-230, 2004 |
■ | Natural killer T-cell activation by OCH, a sphingosine truncated analogue of α-galactosylceramide, prevents collagen-induced arthritis. Chiba A, Oki S, Miyamoto K, Hashimoto H, Yamamura T, Miyake S. Arthr Rheumat 50:305-313, 2004 |
■ | Th2 bias of CD4+ NKT cells derived form multiple sclerosis in remission. Araki M, Kondo T, Gumperz JE, Brenner MB, Miyake S, Yamamura T. Int Immunol 15: 279-288, 2003 |
■ | Functionally distinct subsets of CD1d-restricted natural killer T cells revealed by CD1d tetramer staining. Gumperz JE, Miyake S, Yamamura T, Brenner MB. J Exp Med 195: 625-636, 2002 |
■ | A synthetic glycolipid prevents autoimmune encephalomyelitis by inducing TH2 bias of natural killer T cells. Miyamoto K, Miyake S, Yamamura T. Nature 413:531-534, 2001 |
■ | Natural killer type 2 (NK2) bias in remission of multiple sclerosis. Takahashi K., Miyake S, Kondo T, Terao K, Hatakenaka M, Hashimoto S, Yamamura T. J Clin Invest 107:R23-R29, 2001 |
■ | NR4A2 orchestrates pathogenic Th17 development and initiates autoimmune inflammation. Raveney BJE, Oki S, Yamamura T. PLOS ONE 8: e56595, 2013 |
■ | Interleukin-6 receptor blockade in neuromyelitis optica patients non-responsive to anti-CD20 therapy. Ayzeberg I, Kleiter I, Schroder A, Hellwig K, Chan A, Yamamura T, Gold R. JAMA Neurol online first doi:10:1001/jamaneurol.2013.1246 |
■ | Clinical improvement in a patient with neuromyelitis optica following therapy with the anti-IL-6 receptor monoclonal antibody tocilizumab. Araki M, Aranami T, Matsuoka T, Nakamura M, Miyake S, Yamamura T. Modern Rheumatol published online, (11 July 2012) |
■ | B-cell-directed therapy: which B cells should be targeted and how? http://www.ncbi.nlm.nih.gov/pubmed/22642324 Yamamura T, Miyake S. Immunotherapy 4: 455-457, 2012 |
■ | Mucosal-associated invariant T cells promote inflammation and exacerbate disease in murine models of arthritis. Chiba A, Tajima R, Tomi C, Miyazaki Y, Yamamura T, Miyake S. Arthritis Rheum 64: 153-161, 2012 |
■ | CCR2+CCR5+ T cells produce matrix metalloproteinase-p and osteopontin in the pathogenesis of multiple sclerosis. Sato W, Tomita A, Ichikawa D, Lin Y, Kishida H, Miyake S, Ogawa M, Okamoto T, Murata M, Kuroiwa Y, Aranami T, Yamamura T J Immunol 189: 5057-5065, 2012 |
National Institute of Neuroscience, NCNP
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