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Genetic and immunological analysis for HLA-DP5 and HLA-DR53 related diseases.

Planned Research

Project AreaHLA polymorphism, disease and evolution
Project/Area Number 22133009
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKyushu University

Principal Investigator

SASAZUKI Takehiko  九州大学, 生体防御医学研究所, 特別主幹教授 (50014121)

Co-Investigator(Kenkyū-buntansha) OKAMURA Tadashi  独立行政法人国立国際医療研究センター, 研究所, 室長 (00333790)
TANAKA Yoshihiko  福岡歯科大学, 歯学部, 教授 (00398083)
KISHIKAWA Reiko  独立行政法人国立病院機構福岡病院(臨床研究部), アレルギー科, 医長 (50450945)
MORI Akio  独立行政法人国立病院機構(相模原病院臨床研究センター), 先端技術開発研究部, 部長 (80251247)
OKAMURA Ken  九州大学, 医学研究院, 名誉教授 (90150432)
YOSHIKAI Yasunobu  九州大学, 生体防御医学研究所, 教授 (90158402)
NODA Mitsuhiko  独立行政法人国立国際医療研究センター, 糖尿病研究部, 部長 (90237850)
Research Collaborator ITO Kouichi  
YOSHIMURA Hiroshi  
Project Period (FY) 2010-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥207,740,000 (Direct Cost: ¥159,800,000、Indirect Cost: ¥47,940,000)
Fiscal Year 2014: ¥38,740,000 (Direct Cost: ¥29,800,000、Indirect Cost: ¥8,940,000)
Fiscal Year 2013: ¥40,690,000 (Direct Cost: ¥31,300,000、Indirect Cost: ¥9,390,000)
Fiscal Year 2012: ¥42,640,000 (Direct Cost: ¥32,800,000、Indirect Cost: ¥9,840,000)
Fiscal Year 2011: ¥42,250,000 (Direct Cost: ¥32,500,000、Indirect Cost: ¥9,750,000)
Fiscal Year 2010: ¥43,420,000 (Direct Cost: ¥33,400,000、Indirect Cost: ¥10,020,000)
KeywordsHLA-DP5 / HLA-DR53 / グレーブス病 / 橋本病 / スギ花粉症 / HLA立体構造 / エピスターシス / ゲノム解析 / HLA / 立体構造 / VAV3 / HLA / 自己免疫性甲状腺炎 / DP5 / HLA-DP5 / HLA-DR53 / 花粉症
Outline of Final Research Achievements

We identified Graves disease-specific susceptible HLA alleles, HLA-DR14:03 and DPB1*05:01, and protective alleles, HLA-DRB1*13:02, DRB1*15:02 and B*07:02 by association analysis for HLA-A, B, C, DRB1, DQB1 and DPB1 loci. In addition, we elucidated the epistatic role of protective HLA-DRB1*13:02 allele to susceptible HLA alleles in the incidence of Graves disease. We revealed a crystal structure of the CryJ-1-derived peptide, a major allergen of cedar pollinosis, and HLA-DP5 complex, which would contribute to development of a chemical compound capable of regulating the allergic reaction.

Report

(6 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (20 results)

All 2015 2014 2013 2012 2011 2010 Other

All Journal Article (16 results) (of which Peer Reviewed: 16 results,  Open Access: 1 results,  Acknowledgement Compliant: 3 results) Presentation (3 results) (of which Invited: 2 results) Remarks (1 results)

  • [Journal Article] Associations of HLA class I alleles in Japanese patients with Crohn's disease.2015

    • Author(s)
      102)Oryoji D, Hisamatsu T, Tsuchiya K, Umeno J, Ueda S, Yamamoto K, Matsumoto T, Watanabe M, Hibi T, Sasazuki T.
    • Journal Title

      Genes Immun.

      Volume: 16 Issue: 1 Pages: 54-56

    • DOI

      10.1038/gene.2014.61

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Identification of a Hashimoto thyroiditis susceptibility locus via a genome-wide comparison with Graves' disease.2015

    • Author(s)
      Oryoji D, Ueda S, Yamamoto K, Yoshimura Noh J, Okamura K, Noda M, Watanabe N, Yoshihara A, Ito K, Sasazuki T.
    • Journal Title

      J Clin Endocrinol Metab.

      Volume: 100 Issue: 2 Pages: E319-E324

    • DOI

      10.1210/jc.2014-3431

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Identification of independent susceptible and protective HLA alleles in Japanese autoimmune thyroid disease and their epistasis.2014

    • Author(s)
      Ueda S, Oryoji D, Yamamoto K, Noh JY, Okamura K, Noda M, Kashiwase K, Kosuga Y, Sekiya K, Inoue K, Yamada H, Oyamada A, Nishimura Y, Yoshikai Y, Ito K, Sasazuki T.
    • Journal Title

      J Clin Endocrinol Metab.

      Volume: 99 Issue: 2 Pages: E379-E383

    • DOI

      10.1210/jc.2013-2841

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural Basis for the Specific Recognition of the Major Antigenic Peptide from the Japanese Cedar Pollen Allergen Cry j 1 by HLA-DP5.2014

    • Author(s)
      Kusano S, Kukimoto-Niino M, Satta Y, Ohsawa N, Uchikubo-Kamo T, Wakiyama M, Ikeda M, Terada T, Yamamoto K, Nishimura Y, Shirouzu M, Sasazuki T, Yokoyama S.
    • Journal Title

      J Mol Biol.

      Volume: 426 Issue: 17 Pages: 3016-3027

    • DOI

      10.1016/j.jmb.2014.06.020

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Tyk2-Dependent Bystander Activation of Conventional and Nonconventional Th1 Cell Subsets Contributes to Innate Host Defense against Listeria monocytogenes Infection.2014

    • Author(s)
      Hashiguchi T, Oyamada A, Sakuraba K, Shimoda K, Nakayama KI, Iwamoto Y, Yoshikai Y, Yamada H.
    • Journal Title

      J Immunol.

      Volume: 192 Issue: 10 Pages: 4739-4747

    • DOI

      10.4049/jimmunol.1303067

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Positive selection of self-antigen-specific CD8+ T cells by hematopoietic cells.2013

    • Author(s)
      Yamada H, Shibata K, Sakuraba K, Fujimura K, Yoshikai Y.
    • Journal Title

      Eur J Immunol.

      Volume: 43 Issue: 8 Pages: 2033-2042

    • DOI

      10.1002/eji.201242957

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ZFAT plays critical roles in peripheral T cell homeostasis and its T cell receptor-mediated response.2012

    • Author(s)
      Doi K, Shirasawa S
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 425(1) Issue: 1 Pages: 107-112

    • DOI

      10.1016/j.bbrc.2012.07.065

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protein phosphatase 1 is involved in IL-2-induced IL-5 and IL-13 expression in human T cells.2012

    • Author(s)
      Yamaoka K
    • Journal Title

      Genes to Cells

      Volume: 17 Issue: 7 Pages: 611-618

    • DOI

      10.1111/j.1365-2443.2012.01610.x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DOCK8 is a Cdc42 activator critical for interstitial dendritic cell migrataon during immune responses2012

    • Author(s)
      Yosuke Harada, Yoshihiko Tanaka, Masao Terasawa, Markus Pieczyk, Katsuyoshi Habiro, Tomoya Katakai, Kyoko Hanawa-Suetsugu, Mutsuko Kukimoto-Niino, Tomoko Nishizaki, Mikako Shirouzu, Xuefeng Duan, Takehito Uruno, Akihiko Nishikimi, Fumiyuki Sanematsu, Shigeyuki Yokoyama, Jens V.Stein, Tatsuo Kinashi, Yoshinori Fukui
    • Journal Title

      Blood

      Volume: (In press) Issue: 19 Pages: 4451-4461

    • DOI

      10.1182/blood-2012-01-407098

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Provision of continuous maturation signaling to dendritic cells by RIG-1-stimulating cytosolic RNA synthesis of Sendai virus2011

    • Author(s)
      Okano S,, et al
    • Journal Title

      J Immunol

      Volume: 186 Issue: 3 Pages: 1828-39

    • DOI

      10.4049/jimmunol.0901641

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of independent risk loci for Graves' disease within the MHC in the Japanese population.2011

    • Author(s)
      Nakabayashi K, Shirasawa S
    • Journal Title

      J Hum Genet

      Volume: 56(11) Issue: 11 Pages: 772-778

    • DOI

      10.1038/jhg.2011.99

    • NAID

      10030661591

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ZFAT is a critical molecule for cell survival in mouse embryonic fibroblasts2011

    • Author(s)
      Doi K, et al
    • Journal Title

      Cell Mol Biol Lett

      Volume: 16 Issue: 1 Pages: 89-100

    • DOI

      10.2478/s11658-010-0041-1

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ZFAT is a critical molecule for cell survival in mouse embryonic fibroblasts.2011

    • Author(s)
      Doi K, Shirasawa S
    • Journal Title

      Cell MolBiol Lett

      Volume: 16(1) Issue: 3 Pages: 89-100

    • DOI

      10.1158/0008-5472.can-10-0714

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Ly49Q receptor plays a crucial role in neutrophil polarization and migration by regulating raft trafficking.2010

    • Author(s)
      Sasawatari S, et al.
    • Journal Title

      Immunity

      Volume: 32 Pages: 200-213

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deregulation of the PI3K and KRAS signaling pathways in human cancer cells determines their response to everolimus.2010

    • Author(s)
      Di Nicolantonio F, et al.
    • Journal Title

      J Clin Invest.

      Volume: 120 Pages: 2858-2866

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immune-related zinc finger gene ZFAT is an essential transcriptional regulator for hematopoietic differentiation in blood islands.2010

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

      Proc Natl Acad Sci U S A

      Volume: 107 Pages: 14199-14204

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Immunogenetic risk factors for autoimmune thyroid disease (ZFAT, FcRL3 and HLA).2012

    • Author(s)
      Sasazuki T
    • Organizer
      14th International Congress of Immunology.
    • Place of Presentation
      Kobe, Japan
    • Year and Date
      2012-08-22
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Epistatic interaction between protective HLA alleles and susceptible HLA-DP allele in autoimmune thyroid disease.2012

    • Author(s)
      Sasazuki T
    • Organizer
      16th International HLA and Immunogenetics Workshop and Conference.
    • Place of Presentation
      Liverpool, England
    • Year and Date
      2012-05-28
    • Related Report
      2012 Annual Research Report
  • [Presentation] HLA controls the clinical difference, overlap, and conversion between Graves disease and Hashimoto thyroiditis.2012

    • Author(s)
      Sasazuki T
    • Organizer
      Novo nordisk innovation summit.
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      2012-04-17
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Remarks] 新学術領域研究「HLA進化と疾病」

    • URL

      http://dbhla.jp/HP_sinryoiki/

    • Related Report
      2014 Annual Research Report

URL: 

Published: 2010-08-23   Modified: 2019-07-29  

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