To explore new biomarkers in autoimmune diseases

• Project/Area Number: 23659291
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine
• Research Institution: Tohoku University
• Principal Investigator: OGASAWARA Kouetsu 東北大学, 加齢医学研究所, 教授 (30323603)
• Co-Investigator(Kenkyū-buntansha): ISHII Tomonori 東北大学, 医学系研究科, 准教授 (10282138)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 免疫血清学 / 自己免疫疾患 / NK細胞 / バイオマーカー / 免疫学

Research Abstract

Autoimmune disease is considered to be caused by genetic factors, environmental factors, and the time factor. However, the diagnostic methods including environmental factors and a time factor have not been established. NK cells are known as a group of cells of the innate immune system. NK cell has been examined cell surface molecules and receptors in the view of the elimination of tumor and infection defense. Therefore, until now it has been unknown whether NK receptors and NK cells are involved in autoimmune disease. In this study, we performed experiments on the basis of the original idea by which NK receptors and NK cells are involved in autoimmune diseases. Our purpose was to explore new biomarkers of autoimmune diseases, such as systemic lupus erythematosus (SLE) and type I diabetes for a diagnostic index.In this study we found that NKG2D ligands that do not express almost normal tissues isabnormally expressed in autoimmune disease model mice, and autoreactive T cells had abnormally express NKG2D. Therefore, these results suggest that NKG2D ligand isavailable as a new biomarker in type I diabetes.

Research Products

• [Journal Article] Fratricide of natural killer cells dressed with tumor-derived NKG2D ligand (2013)
  • Author(s): Nakamura K, Nakayama M, Kawano M, Amagai R, Ishii T, Harigae H, Ogasawara K
  • Journal Title: Proc Natl Acad Sci U S A Volume: 110(23) Pages: 9421-9426
  • Peer Reviewed
• [Journal Article] Fratricide of natural killer cells dressed with tumor-derived NKG2D ligand (2013)
  • Author(s): Nakamura K, Nakayama M, Kawano M, Amagai R, Ishii T, Harigae H, Ogasawara K.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: in press
  • Peer Reviewed
• [Journal Article] Inhibitory receptor PIR-B is exploited by Staphylococcus aureus for virulence (2012)
  • Author(s): Nakayama M, Kurokawa K, Nakamura K, Lee BL, Sekimizu K, Kubagawa H, Hiramatsu K, Yagita H, Okumura K, Takai T, Underhill DM, Aderem A, Ogasawara K.
  • Journal Title: J Immunol Volume: 189 Issue: 12 Pages: 5903-5911
  • DOI: 10.4049/jimmunol.1201940
  • Peer Reviewed
• [Journal Article] A new method for quantitative analysis of the T cell receptor V region repertoires in healthy common marmosets by microplate hybridization assay (2012)
  • Author(s): Kitaura K, Fujii Y, Matsutani T, Shirai K, Suzuki S, Takasaki T, Shimada S, Kametani Y, Shiina T, Takabayashi S, Katoh H, Ogasawara K, Kurane I, Suzuki R
  • Journal Title: Journal of Immunological Methods Volume: 384 Pages: 81-91
  • URL: http://dx.doi.org/10.1016/j.jim.2012.07.012
  • Peer Reviewed
• [Journal Article] A group of atopic dermatitis without IgE elevation or barrier impairment shows a high Th1 frequency: Possible immunological state of the intrinsic type (2012)
  • Author(s): Kabashima-Kubo R, Nakamura M, Sakabe, J, Sigita K, Hino R, Mori T, Kobayashi M, Bito T, Kabashima K, Ogasawara K, Nomura Y, Nomura T, Akiyama M, Shimizu H, Tokura Y
  • Journal Title: J Dermatol Sci Volume: 67 Pages: 37-43
  • URL: http://dx.doi.org/10.1016/j.jdermsci.2012.04.004
  • Peer Reviewed
• [Journal Article] Blocking of CTLA-4 on lymphocytes improves the sensitivity of lymphocyte transformation tests in a patient with nickel allergy (2012)
  • Author(s): Sugita K, Kabashima K, Sawada Y, Haruyama S, Yoshioka M, Mori T, Kobayashi M, Ogasawara K, Tokura Y.
  • Journal Title: Eur J Dermatol Volume: 22(2) Issue: 2 Pages: 268-269
  • DOI: 10.1684/ejd.2012.1641
  • Peer Reviewed
• [Journal Article] NK-dendritic cell interactions generate MHC class II-dressed NK cells that regulate CD4^+ T cells (2011)
  • Author(s): Nakayama M, Takeda K, Kawano M, TakaiT, Ishii N, Ogasawara K
  • Journal Title: Proc Natl Acad Sci U S A Volume: 108 (45) Pages: 18360-18365
  • Peer Reviewed
• [Journal Article] Increased positive selection pressure within the CDR regions of the T cell receptor β gene in New World monkeys (2011)
  • Author(s): Matsutani T, Fujii Y, Kitaura K, Suzuki S, Tsuruta Y, Itoh T, Nishimoto N, Takasaki T, Kurane I, Suzuki R
  • Journal Title: Am J Primatol Volume: 73 Issue: 10 Pages: 1082-1092
  • DOI: 10.1002/ajp.20976
  • Peer Reviewed
• [Journal Article] SPRY domain-containing SOCS box protein-1 (SPSB1), SPSB2, and SPSB4 are master regulators of proteasome-dependent degradation of iNOS (2011)
  • Author(s): Nishiya, T., Matsumoto, K., Maekawa, S., Horinouchi, T., Fujimuro, M., Ogasawara, K., Uehara, T., and Miwa, S
  • Journal Title: J. Biol. Chem Volume: 286 Issue: 11 Pages: 9009-9019
  • DOI: 10.1074/jbc.m110.190678
  • Peer Reviewed
• [Journal Article] NK-dendritic cell interactions generate MHC class II-dressed NK cells that regulate CD4+ T cells. (2011)
  • Author(s): Nakayama M, Takeda K, Kawano M, Takai T, Ishii N, Ogasawara K.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 108 Pages: 18360-18365
  • Peer Reviewed
• [Journal Article] IFN-γ production by lung NK cells is critical for the natural resistance to pulmonary metastasis of B16 melanoma in mice. (2011)
  • Author(s): Takeda K, Nakayama M, Sakaki M, Hayakawa Y, Imawari M, Ogasawara K, Okumura K, Smyth MJ.
  • Journal Title: Journal of Leukocyte Biology Volume: 90 Pages: 777-785
• [Presentation] NK細胞の生物学 (2011)
  • Author(s): OgasawaraK
  • Organizer: 第59回東北歯学会
  • Place of Presentation: 仙台
  • Year and Date: 2011-06-10
• [Presentation] Natural killer (NK)-dendritic cell interactions generate MHC class II-dressed NK cells that regulate CD4+ T cells (2011)
  • Author(s): Nakayama M, Takeda K, Kawano M, Takai T, Ishii N, and Ogasawara K
  • Organizer: 第40回 日本免疫学会総会
  • Place of Presentation: 千葉
• [Book] 炎症と免疫 (2013)
  • Author(s): 小笠原康悦
  • Publisher: 先端医学社
• [Remarks]
  • URL: http://www2.idac.tohoku.ac.jp/dep/imbio/