Study on roles of circadian clock gene in allergic immune response

• Project/Area Number: 24590088
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Jichi Medical University
• Principal Investigator: KASHIWADA MASAKI 自治医科大学, 医学部, 准教授 (20270639)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 時計遺伝子 / アレルギー / 喘息 / 肥満細胞 / アナフィラキシー / Th2

Outline of Final Research Achievements

Although many studies have indicated that allergic attack and symptoms were most severe in the early morning, the precise mechanisms by which the circadian clock regulates the time of day-dependent phenotypes in allergic reaction are still unknown. We investigated the roles of the circadian clock gene NFIL3 in the allergic immune responses using NFIL3-deficient mice. In NFIL3-deficient mice, enhanced infiltration of inflammatory cells and development of airway hyperresponsiveness were observed in a mouse asthma model. Ablation of NFIL3 expression limited mast cell functions including cytokine production but did not impact on the development of mast cells.

Research Products

• [Journal Article] NFIL3-Deficient Mice Develop Microbiota-Dependent, IL-12/23-Driven Spontaneous Colitis. (2014)
  • Author(s): Kobayashi, T., Steinbach, E.C., Russo, S.M., Matsuoka, K., Nochi, T., Maharshak, N., Borst, L.B., Hostager, B., Garcia-Martinez, J.V., Rothman, P.B., Kashiwada, M., Sheikh, S.Z., Murray, P.J. and Plevy, S.E.
  • Journal Title: Journal of Immunology Volume: 192 Issue: 4 Pages: 1918-1927
  • DOI: 10.4049/jimmunol.1301819
  • Peer Reviewed
• [Journal Article] TH17 cell differentiation is regulated by the circadian clock. (2013)
  • Author(s): Yu, X., Rollins, D., Ruhn, K.A., Stubblefield, J.J., Green, C.B., Kashiwada, M., Rothman, P.B., Takahashi, J.S., and Hooper, L.V.
  • Journal Title: Science Volume: 342 Issue: 6159 Pages: 727-730
  • DOI: 10.1126/science.1243884
  • Peer Reviewed
• [Journal Article] A requirement for SOCS-1 and SOCS-3 phosphorylation in Bcr-Abl-induced tumorigenesis (2012)
  • Author(s): Xiaoxue Qiu, Guijie Guo, Ke Chen, Masaki Kashiwada, Brian Druker, Paul Rothman and Jilong Chen
  • Journal Title: Neoplasia Volume: 14 Issue: 6 Pages: 547-558
  • DOI: 10.1596/neo.12230
  • Peer Reviewed
• [Presentation] NFIL3 suppresses Rorγt transcription and links intestinal Th17 cell differentiation to the circadian clock network. (2013)
  • Author(s): 1) Yu, X., Rollins, D., Kashiwada, M., Rothman, P., Takahashi, J. and Hooper, L.
  • Organizer: IMMUNOLOGY 2013
  • Place of Presentation: Honolulu, USA
• [Presentation] NFIL3 suppresses Rorγt transcription and links intestinal Th17 cell differentiation to the circadian clock network. (2013)
  • Author(s): 2) Yu, X., Rollins, D., Kashiwada, M., Rothman, P., Takahashi, J. and Hooper, L.
  • Organizer: 78th Cold Spring Harbor Symposium on Quantitative Biology; Immunity & Tolerance.
  • Place of Presentation: Cold Spring Harbor Laboratory, New York, USA
• [Presentation] NFIL3 deficient mice develop IL-12/23 driven spontaneous colitis. (2013)
  • Author(s): 3) Kobayashi, T., Russo, S.M., Matsuoka, K., Nochi, T., Maharshak, N., Borst, L.B., Hostager, B., Garcia-Martinez, J.V., Rothman, P.B., Kashiwada, M., Murray, P.J., Plevy, S.E.
  • Organizer: 1st Annual Meeting of Asian Organization for Crohn’s & Colitis
  • Place of Presentation: 東京
• [Presentation] サイトカイン誘導性転写因子NFIL3/E4BP4によるTh2反応制御 (2013)
  • Author(s): 柏田正樹、Suzanne Cassel, John Colgan, Paul Rothman
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: パシフィコ横浜
• [Presentation] Lineage-specific regulation of natural killer cell development and function by the transcription factor NFIL3/E4BP4 (2012)
  • Author(s): Kashiwada, M., Heusel, J.W. and Rothman, P.B.
  • Organizer: Cold Spring Harbor Laboratory Meeting; Gene Expression and Signaling in the Immune System
  • Place of Presentation: Cold Spring Harbor Laboratory (New York)
• [Presentation] NFIL3 deficient mice develop severe innate immune mediated spontaneous colitis (2012)
  • Author(s): Kobayashi, T., Russo, S., Matsuoka, K. Nochi, T., Borst, L.B., Garcia, J.V., Rothman, P.B., Kashiwada, M. and Plevy, S.E.
  • Organizer: Digestive Disease Week (DDW) 2012
  • Place of Presentation: San Diego Convention Center (San Diego)