A study on the development of new strategy to control inflammation using molecular mechanism of a IL-17 high-producing cell line

• Project/Area Number: 23659500
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Kyoto University
• Principal Investigator: USUI Takashi 京都大学, 医学研究科, 非常勤講師 (90362483)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: IL-17 / マイクロアレイ / エピジェネティック制御 / ChiP 解析 / エピジェネティック / ChiP解析 / 炎症 / エピゲノム制御

Research Abstract

IL-17 is an important cytokine in the pathogenesis of autoimmune inflammatory disease, including collagen disease. We established stable murine T cell clones which produce a large amount of IL-17 as well as its low producer from the same T cell line. Then we can analyzed its molecular mechanisms by DNA sequence, RNA (microarray) and epigenetic levels. Although we could not differences in DNA sequence in the promoter region and the expressions of transcriptional factors, we found methylationand de-methylation status were quite different in these clones. Furthermore, we found gene-X could control it. These findings will lead to new-generation strategy for controlling autoimmune inflammatory disease, including collagen disease.

Research Products

• [Journal Article] Three Groups in the 28 Joints for Rheumatoid Arthritis Synovitis - Analysis Using More than 17,000 Assessments in the KURAMA Database. (2013)
  • Author(s): Terao C, Hashimoto M, Yamamoto K, Murakami K, Ohmura K, Nakashima R, Yamakawa N, Yoshifuji H, Yukawa N, Kawabata D, Usui T, Yoshitomi H, Furu M, Yamada R, Matsuda F, Ito H, Fujii T, Mimori T
  • Journal Title: PLoS One Volume: 8(3)
  • NAID: 120005244457
• [Journal Article] NEFA/nucleobindin-2 is a target autoantigen of the anti-Wa antibody and is associated with transfer RNA (2012)
  • Author(s): Imura Y, Shirai Y, Nojima T, Nakashima R, Yamagata H, Miyachi K, Yoshifuji H, Kawabata D, Ohmura K, Usui T, Fujii T, Mimori T
  • Journal Title: Mod Rheumatol Volume: 22(5) Pages: 685-94
  • NAID: 10031027691
• [Journal Article] Follistatin-related protein /follistatin-like 1 evokes an innate immune response via CD14 and toll-like receptor4 (2012)
  • Author(s): Murakami K, Tanaka M, Usui T, Kawabata D, Shiomi A, Iguchi-Hashimoto M, Shimizu M, Yukawa N, Yoshifuji H, Nojima T, Ohmura K, Fujii T, Umehara H, Mimori T
  • Journal Title: FEBS Lett Volume: 586(4) Pages: 319-24
• [Journal Article] Correlation of antinuclear antibody and anti-double-stranded DNA antibody with clinical response to infliximab in patients with rheumatoid arthritis: a retrospective clinical study (2011)
  • Author(s): Yukawa N, Fujii T, Kondo-Ishikawa S, Yoshifuji H, Kawabata D, Nojima T, Ohmura K, Usui T, Mimori T
  • Journal Title: Arthritis Res Ther Volume: 13(6)
  • NAID: 120004754356
• [Journal Article] Overexpression of a minimal domain of calpastatin suppresses IL-6 production and Th17 development via reduced NF- κB and increased STAT5 signals (2011)
  • Author(s): Iguchi-Hashimoto M, Usui T, Yoshifuji H, Shimizu M, Kobayashi S, Ito Y, Murakami K, Shiomi A, Yukawa N, Kawabata D, Nojima T, Ohmura K, Fujii T, Mimori T
  • Journal Title: PLoS One Volume: 6(10)
• [Journal Article] Myelin basic protein as a novel genetic risk factor in rheumatoid arthritis--a genome-wide study combined with immunological analyses. (2011)
  • Author(s): Terao C, Ohmura K, Katayama M, Takahashi M, Kokubo M, Diop G, Toda Y, Yamamoto N
  • Journal Title: PLoS One Volume: 6(6)
• [Journal Article] Interferon-gamma release assay for diagnosing Mycobacterium tuberculosis infections in patients with systemic lupus erythematosus (2011)
  • Author(s): Takeda N, Nojima T, Terao C, Yukawa N, Kawabata D, Ohmura K, Usui T, Fujii T, Ito Y, Iinuma Y, Mimori T
  • Journal Title: Lupus Volume: 20(8) Pages: 792-800
• [Journal Article] The human AIRE gene at chromosome 21q22 is a genetic determinant for the predisposition to rheumatoid arthritis in Japanese population (2011)
  • Author(s): Terao C, Yamada R, Ohmura K, Takahashi M, Kawaguchi T, Kochi Y
  • Journal Title: Hum Mol Genet Volume: 20(13) Pages: 2680-5
• [Journal Article] A case of antisynthetase syndrome in a rheumatoid arthritis patient with anti-PL-12 antibody following treatment with etanercept (2011)
  • Author(s): Ishikawa Y, Yukawa N, Kawabata D, Ohmura K, Fujii T, Usui T, Mimori T
  • Journal Title: Clin Rheumatol Volume: 30(3) Pages: 429-32
  • NAID: 120003039177