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Mechanisms and their regulation of autoimmune disorders

Planned Research

Project AreaImmunological Self Recognition and its Disorders
Project/Area Number 19059005
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe University of Tokyo

Principal Investigator

YAMAMOTO Kazuhiko  東京大学, 医学部附属病院, 教授 (80191394)

Co-Investigator(Kenkyū-buntansha) ISHII Naoto  東北大学, 医学系研究科, 教授 (60291267)
Project Period (FY) 2007 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥157,500,000 (Direct Cost: ¥157,500,000)
Fiscal Year 2011: ¥31,500,000 (Direct Cost: ¥31,500,000)
Fiscal Year 2010: ¥31,500,000 (Direct Cost: ¥31,500,000)
Fiscal Year 2009: ¥31,500,000 (Direct Cost: ¥31,500,000)
Fiscal Year 2008: ¥31,500,000 (Direct Cost: ¥31,500,000)
Fiscal Year 2007: ¥31,500,000 (Direct Cost: ¥31,500,000)
Keywords遺伝学 / 生体分子 / 病理学 / 免疫学 / 臨床 / 遺伝子
Research Abstract

We have observed that in the presence of strong proliferation of antigen-X-specific T cells, co-existing T cells specific to antigen-Y exhibit activation in response to small amount of antigen-Y. We termed this phenomenon as 'Extended antigen presentation (EAP)', a new mechanism of naive T cell activation. This project revealed that the induction of EAP depends on cell-cell contact and the amount of EAP-inducing antigen is as small as that of physiological autoantigen. Moreover, the fact that EAP induction was observed in three different T cell receptor transgenic T cells suggested universal nature of this phenomenon. EAP may be an immunological basis for epitope-spreading in autoimmune disease, and our observation could contribute to the understanding of autoimmunity and the development of therapeutic strategy.

Report

(6 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report   Self-evaluation Report ( PDF )
  • 2008 Annual Research Report
  • Research Products

    (36 results)

All 2012 2011 2010 2009 2008 2007

All Journal Article (35 results) (of which Peer Reviewed: 27 results) Presentation (1 results)

  • [Journal Article] Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population2012

    • Author(s)
      Okada Y, Terao C, Ikari K, Kochi Y, Ohmura K, Suzuki A, Kawaguchi T, Stahl EA, Kurreeman FA, Nishida N, Ohmiya H, Myouzen K, Takahashi M, Sawada T, Nishioka Y, Yukioka M, Matsubara T, Wakitani S, Teshima R, Tohma S, Takasugi K, Shimada K, Murasawa A, Honjo S, Matsuo K, Tanaka H, Tajima K, Suzuki T, Iwamoto T, Kawamura Y, Tanii H, Okazaki Y, Sasaki T, Gregersen PK, Padyukov L, Worthington J, Siminovitch KA, Lathrop M, Taniguchi A, Takahashi A, Tokunaga K, Kubo M, Nakamura Y, Kamatani N, Mimori T, Plenge RM, Yamanaka H, Momohara S, Yamada R, Matsuda F, Yamamoto K.
    • Journal Title

      Nat Genet.

      Volume: (in press) Issue: 5 Pages: 511-6

    • DOI

      10.1038/ng.2231

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of histone modification and chromatin structure by the p53-PADI4 pathway2012

    • Author(s)
      Tanikawa C, Espinosa M, Suzuki A, Masuda K, Yamamoto K, Tsuchiya E, Ueda K, Daigo Y, Nakamura Y, Matsuda K.
    • Journal Title

      Nat Commun.

      Volume: 3 Issue: 1 Pages: 676-676

    • DOI

      10.1038/ncomms1676

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] A genome-wide association study identified AFF1 as a susceptibility locus for systemic lupus eyrthematosus in Japanese2012

    • Author(s)
      岡田随象
    • Journal Title

      PLoS Genetics

      Volume: (掲載確定) Issue: 1 Pages: 1002455-1002455

    • DOI

      10.1371/journal.pgen.1002455

    • NAID

      120005906866

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Induction of human humoral immune responses in a novel HLA-DR-expressing transgenic NOD/Shi-scid/γc^<null> mouse2012

    • Author(s)
      Suzuki M, Takahashi T, Katano I, Ito R, Ito M, Harigae H, Ishii N, Sugamura K.
    • Journal Title

      Int Immunol

      Volume: 24 Issue: 4 Pages: 243-52

    • DOI

      10.1093/intimm/dxs045

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] PADI4 polymorphism predisposes male smokers to rheumatoid arthritis2011

    • Author(s)
      Kochi Y, Thabet MM, Suzuki A, Okada Y, Daha NA, Toes REM, Huizinga TWJ, Myouzen K, Kubo M, Yamada R, Nakamura Y, Yamamoto K.
    • Journal Title

      Ann Rheum Dis

      Volume: 70 Issue: 3 Pages: 512-5

    • DOI

      10.1136/ard.2010.130526

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Indispensable roles of OX40L-derived signal and epistatic genetic effect in immune-mediated pathogenesis of spontaneous pulmonary hypertension2011

    • Author(s)
      Rabieyousefi M, Soroosh P, Satoh K, Date F, Ishii N, Yamashita M, Oka M,McMurtry IF, Shimokawa H, Nose M, Sugamura K, Ono M.
    • Journal Title

      Immunol

      Volume: 12 Issue: 1 Pages: 67-67

    • DOI

      10.1186/1471-2172-12-67

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Interaction between NK cells and dendritic cells generate MHC class II-dressed NK cells to regulate CD4^+ T cells2011

    • Author(s)
      Nakayama M, Takeda K, Kawano M, Takai T, Ishii N, Ogasawara K.
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: 108 Pages: 18360-5

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/22042851

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of osteopontin and its signaling molecule CD44 in clinicopathological features of adult T cell leukemia2011

    • Author(s)
      Chagan-Yasutan H, Tsukasaki K, Takahashi Y, Oguma S, Harigae H, Ishii N, Zhang J, Fukumoto M, Hattori T.
    • Journal Title

      Leuk Res.

      Volume: 35 Issue: 11 Pages: 1484-90

    • DOI

      10.1016/j.leukres.2011.05.011

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Interaction between NK cells and dendritic cells generate MHC class II-dressed NK cells to regulate CD4^+ T cells2011

    • Author(s)
      Nakayama M, Takeda K, Kawano M, Takai T, Ishii N, Ogasawara K
    • Journal Title

      Proc.Natl.Acad.Sci.USA

      Volume: 108 Pages: 18360-5

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PADI4 polymorphism predisposes male smokers to rheumatoid arthritis.2011

    • Author(s)
      Kochi Y, Thabet MM, Suzuki A, Okada Y, Daha NA, Toes REM, Huizinga TWJ, Myouzen K, Kubo M, Yamada R, Nakamura Y, Yamamoto K.
    • Journal Title

      Ann Rheum Dis

      Volume: 70 Pages: 512-515

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The family of IL-10 secreting CD4+ T cells2010

    • Author(s)
      Fujio K, Okamura T, Yamamoto K.
    • Journal Title

      Advances in Immunology

      Volume: 05 Pages: 99-130

    • DOI

      10.1016/s0065-2776(10)05004-2

    • ISBN
      9780123813022
    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility2010

    • Author(s)
      Kochi Y, Okada Y, Suzuki A, Ikari K, Terao C, Takahashi A, Yamazaki K, Hosono N, Myouzen K, Tsunoda T, Kamatani N, Furuichi T, Ikegawa S, Ohmura K, Mimori T, Matsuda F, Iwamoto T, Momohara S, Yamanaka H, Yamada R, Kubo M, Nakamura Y, Yamamoto K.
    • Journal Title

      Nat Genet.

      Volume: 42 Issue: 6 Pages: 515-9

    • DOI

      10.1038/ng.583

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] OX40 ligand plays an important role in the development of atherosclerosis through vasa vasorum neovascularization2010

    • Author(s)
      Nakano M, Fukumoto Y, Satoh K, Ito Y, Kagaya Y, Ishii N, Sugamura K, Shimokawa H.
    • Journal Title

      Cardiovasc Res.

      Volume: 88 Issue: 3 Pages: 539-46

    • DOI

      10.1093/cvr/cvq211

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Serial OX40 engagement on CD4+ T cells and natural killer T cells causes allergic airway inflammation2010

    • Author(s)
      Damayanti T, Kikuchi T, Zaini J, Daito H, Kanehira M, Kohu K, Ishii N, Satake M, Sugamura K, Nukiwa T.
    • Journal Title

      Am J Respir Crit Care Med.

      Volume: 181 Issue: 7 Pages: 688-98

    • DOI

      10.1164/rccm.200910-1598oc

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The association of a nonsynonymous single-nucleotide polymorphism in TNFAIP3 with systemic lupus erythematosus and rheumatoid arthritis in the Japanese population2010

    • Author(s)
      Shimane K, Kochi Y, Horita T, Ikari K, Amano H, Hirakata M, Okamoto A, Yamada R, Myouzen K, Suzuki A, Kubo M, Atsumi T, Koike T, Takasaki Y, Momohara S, Yamanaka H, Nakamura Y, Yamamoto K.
    • Journal Title

      Arthritis Rheum.

      Volume: 62 Issue: 2 Pages: 574-9

    • DOI

      10.1002/art.27190

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The family of IL-10 secreting CD4+ T cells.2010

    • Author(s)
      Fujio K, Okamura T, Yamamoto K.
    • Journal Title

      Advances in Immunology.

      Volume: 105 Pages: 99-130

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility.2010

    • Author(s)
      Kochi Y, Okada Y, Suzuki A, Ikari K, Terao C, Takahashi A, Yamazaki K, Hosono N, Myouzen K, Tsunoda T, Kamatani N, Furuichi T, Ikegawa S, Ohmura K, Mimori T, Matsuda F, Iwamoto T, Momohara S, Yamanaka H, Yamada R, Kubo M, Nakamura Y, Yamamoto K.
    • Journal Title

      Nat Genet.

      Volume: 42 Pages: 515-519

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] OX40 ligand plays an important role in the development of atherosclerosis through vasa vasorum neovascularization.2010

    • Author(s)
      Nakano, M., et al
    • Journal Title

      Cardiovasc.Res.

      Volume: 88 Pages: 539-546

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serial OX40 engagement on CD4^+ T cells and NKT cells causes allergic airway inflammation.2010

    • Author(s)
      Damayanti, T., et al.
    • Journal Title

      Am.J.Respir.Crit.Care.Med.

      Volume: 181 Pages: 688-698

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The association of a nonsynonymous single-nucleotide polymorphism in TNFAIP3 with systemic lupus erythematosus and rheumatoid arthritis in the Japanese population.2010

    • Author(s)
      Shimane K, Kochi Y, Horita T, Ikari K, Amano H, Hirakata M, Okamoto A, Yamada R, Myouzen K, Suzuki A, Kubo M, Atsumi T, Koike T, Takasaki Y, Momohara S, Yamanaka H, Nakamura Y, Yamamoto K.
    • Journal Title

      Arthritis Rheum. 62

      Pages: 574-579

    • Related Report
      2009 Self-evaluation Report
  • [Journal Article] The association of a nonsynonymous single-nucleotide polymorphism in TNFAI P3 with systemic lupus erythematosus and rheumatoid arthritis in the Japanese population2010

    • Author(s)
      Shimane K, Kochi Y, Horita T, Ikari K, Amano H, Hirakata M, Okamoto A, Yamada R, Myouzen K, Suzuki A, Kubo M, Atsumi T, Koike T, Takasaki Y, Momohara S, Yamanaka H, Nakamura Y, Yamamoto K.
    • Journal Title

      Arthritis Rheum 62

      Pages: 574-79

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A single nucleotide polymorphism in the IRF5 promoter region is associated with susceptibility to rheumatoid arthritis in the Japanese population2009

    • Author(s)
      Shimane K, Kochi Y, Yamada R, Okada Y, Suzuki A, Miyatake A, Kubo M, Nakamura Y, Yamamoto K.
    • Journal Title

      Ann Rheum Dis.

      Volume: 68 Issue: 3 Pages: 377-83

    • DOI

      10.1136/ard.2007.085704

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] A single nucleotide polymorphism in the IRF5 promoter region is associated with susceptibility to rheumatoid arthritis in the Japanese population.2009

    • Author(s)
      Shimane K, Kochi Y, Yamada R, Okada Y, Suzuki A, Miyatake A, Kubo M, Nakamura Y, Yamamoto K.
    • Journal Title

      Ann Rheum Dis. 68

      Pages: 377-83

    • Related Report
      2009 Self-evaluation Report
  • [Journal Article] FCRL3, an autoimmune susceptibility gene, has inhibitory potential on B-cell receptor-mediated signaling.2009

    • Author(s)
      Kochi Y, Myouzen K, Yamada R, Suzuki A, Kurosaki T, Nakamura Y, Yamamoto K.
    • Journal Title

      J Immunol. 183

      Pages: 5502-10

    • Related Report
      2009 Self-evaluation Report
  • [Journal Article] Contribution of a haplotype in the HLA region to anti-cyclic citrullinated peptide antibody positivity in rheumatoid arthritis, independently of HLA-DRB1.2009

    • Author(s)
      Okada Y, Yamada R, Suzuki A, Kochi Y, Shimane K, Myouzen K, Kubo M, Nakamura Y, Yamamoto K.
    • Journal Title

      Arthritis Rheum. 60

      Pages: 3582-3590

    • Related Report
      2009 Self-evaluation Report
  • [Journal Article] CD4+CD25-LAG3+ regulatory T cells controlled by the transcription factor Egr-2.2009

    • Author(s)
      Okamura T, Fujio K, Shibuya M, Sumitomo S, Shoda H, Sakaguchi S, Yamamoto K.
    • Journal Title

      Proc Natl Acad Sci USA. 106

      Pages: 13974-79

    • Related Report
      2009 Self-evaluation Report
  • [Journal Article] A single nucleotide polymorphism in the IRF5 promoter region is associated with susceptibility to rheumatoid arthritis in the Japanese population2009

    • Author(s)
      Shimane K, Kochi Y, Yamada R, Okada Y, Suzuki A, Miyatake A, Kubo M, Nakamura Y, Yamamoto K.
    • Journal Title

      Ann Rheum Dis 68

      Pages: 377-83

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional SNPs in CD244 gene increase the risk of rheumatoid arthritis in a Japanese population2008

    • Author(s)
      Suzuki A,Yamada R, Kochi Y, Sawada T, Okada Y, Matsuda K, Kamatani Y, Mori M, Shimane K, Takahashi A, Tsunoda T, Miyatake A, Kubo M, Kamatani N, Nakamura Y, Yamamoto K
    • Journal Title

      Nat Genet.

      Volume: 40 Pages: 1224-9

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] OX40 costimulatory signals potentiate the memory commitment of effector CD8+ T cells2008

    • Author(s)
      Mousavi SF, Soroosh P, Takahashi T, Yoshikai Y, Shen H, Lefrancois L, Borst J, Sugamura K, Ishii N.
    • Journal Title

      J Immunol.

      Volume: 181 Pages: 5990-6001

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/18941188

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Splenic phagocytes promote responses to nucleosomes in (NZB x NZW) F1 mice.2008

    • Author(s)
      Okamoto A, Fujio K, van Rooijen N, Tsuno NH, Takahashi K, Tsurui H, Hirose S, Elkon KB, Yamamoto K.
    • Journal Title

      J Immunol. 181

      Pages: 5264-71

    • Related Report
      2009 Self-evaluation Report
  • [Journal Article] Functional SNPs in CD244 gene increase the risk of rheumatoid arthritis in a Japanese population.2008

    • Author(s)
      Suzuki A, Yamada R, Kochi Y, Sawada T, Okada Y, Matsuda K, Kamatani Y, Mori M, Shimane K, Takahashi A, Tsunoda T, Miyatake A, Kubo M, Kamatani N, Nakamura Y, Yamamoto K
    • Journal Title

      Nat Genet. 40

      Pages: 1224-9

    • Related Report
      2009 Self-evaluation Report
  • [Journal Article] Lessons from a Genomewide Association Study of Rheumatoid Arthritis.2007

    • Author(s)
      Yamamoto K, Yamada R.
    • Journal Title

      N. Engl. J. Med. 357

      Pages: 1250-1251

    • Related Report
      2009 Self-evaluation Report
  • [Journal Article] Hepatocyte growth factor significantly suppresses collagen-induced Hepatocyte growth factor significantly suppresses collagen-induced arthritis in mice arthritis in mice.2007

    • Author(s)
      Okunishi K, Dohi M, Fujio K, Nakagome K, Yamamoto K, 他7名
    • Journal Title

      J Immunol. 179

      Pages: 5504-5513

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lessons from a Genomewide Association Study of Rheumatoid Arthritis.2007

    • Author(s)
      Yamamoto K, Yamada R.
    • Journal Title

      N.Engl J.Med 357

      Pages: 1250-1251

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interleukin-17B and interleukin-17C are associated with TNF-alpha Production and contribute to the exacerbation of inflammatory arthritis.2007

    • Author(s)
      Yamaguchi Y, Fujio K, Shoda H, Okamoto A, Yamamoto K., 他2名
    • Journal Title

      J Immunol 179

      Pages: 7128-7136

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] OX40 contributes to the generation and maintenance of memory CD4+ T cells2011

    • Author(s)
      Ishii N.
    • Organizer
      第40回日本免疫学会学術集会国際シンポジウム
    • Place of Presentation
      千葉市
    • Year and Date
      2011-11-29
    • Related Report
      2011 Annual Research Report 2011 Final Research Report

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Published: 2007-04-01   Modified: 2018-03-28  

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