Elucidation of the regulatory T cell induction mechanism by IL-27 -towards novel therapy for SLE-

• Project/Area Number: 25860803
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: The University of Tokyo
• Principal Investigator: IWASAKI Yukiko 東京大学, 医学部附属病院, 助教 (30592935)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: IL-27 / 制御性T細胞 / Egr2 / 制御性Ｔ細胞 / 全身性エリテマトーデス / LAG3

Outline of Final Research Achievements

We have recently reported the CD4+CD25-LAG3+ new regulatory T cells (LAG3 Treg), which specifically express the transcriptional factor early response gene 2 (Egr2). The applicant has already found that interleukin　(IL)-27 cytokine can induce both Egr2 and LAG3 on naive CD4-positive T cells. In this project, it was shown that the IL-27-induced CD4-positive T cells can suppress antibody production from B cells. In addition, the applicant revealed that IL-27 signal can be transduced by the transcriptional factor signal transducer and activator of transcription 3 (STAT3), resulting in Egr2 expression. These findings provide insights into the novel therapeutic potential for systemic lupus erythematosus (SLE).

Research Products

• [Journal Article] TGF-β3-expressing CD4+CD25(-)LAG3+ regulatory T cells control humoral immune responses (2015)
  • Author(s): Okamura T, Sumitomo S, Morita K, Iwasaki Y, Inoue M, Nakachi S, Komai T, Shoda H, Miyazaki J, Fujio K, Yamamoto K.
  • Journal Title: Nature Communications Volume: 6 Issue: 1 Pages: 1-14
  • DOI: 10.1038/ncomms7329
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Interleukin-27 in T cell immunity. (2015)
  • Author(s): Iwasaki Y, Fujio K, Okamura T, Yamamoto K
  • Journal Title: Int J Mol Sci Volume: 16 Issue: 2 Pages: 2851-63
  • DOI: 10.3390/ijms16022851
  • Peer Reviewed / Open Access
• [Journal Article] Egr-2 transcription factor is required for Blimp-1 mediated IL-10 production in IL-27 stimulated CD4(+) T cells (2013)
  • Author(s): Iwasaki, Y.
  • Journal Title: Eur J Immunol Volume: undefined Issue: 4 Pages: 1063-73
  • DOI: 10.1002/eji.201242942
  • Peer Reviewed
• [Journal Article] IL-27による免疫制御機構 (2013)
  • Author(s): 岩崎由希子
  • Journal Title: 臨床免疫・アレルギー科 Volume: 59 Pages: 282-287
• [Journal Article] Toward therapeutic application of IL-10-producing regulatory T cells (2013)
  • Author(s): Yukiko Iwasaki, Keishi Fujio, Tomohisa Okamura, Atsushi Yanai, Kazuhiko Yamamoto
  • Journal Title: Nihon Rinsho Meneki Gakkai Kaishi Volume: 36 Pages: 40-46
• [Presentation] IL-27 induces regulatory T cells that suppress B cell responses (2014)
  • Author(s): Y. Iwasaki, T. Okamura, K.Morita, M. Inoue, S. Sumitomo, K. Fujio, K. Yamamoto1
  • Organizer: 第43会日本免疫学会学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Transcription factor Egr-2 mediates IL-27-induced IL-10 production in CD4+ T cells (2013)
  • Author(s): Yukiko Iwasaki, Keishi Fujio, Tomohisa Okamura, Atsushi Yanai, Shuji Sumitomo, Tomohiko Tamura, Hiroki Yoshida, Kazuhiko Yamamoto
  • Organizer: 第5回EAGOR (East Asian Group of Rheumatology) meeting
  • Place of Presentation: The Plaza, Seoul, Korea
• [Presentation] Novel IL-10 induction pathway mediated by Egr-2 in IL-27-stimulated T cells (2013)
  • Author(s): Yukiko Iwasaki, Keishi Fujio, Tomohisa Okamura, Atsushi Yanai, Shuji Sumitomo, Hirofumi Shoda, Kazuhiko Yamamoto
  • Organizer: 第57回日本リウマチ学会総会・学術集会
  • Place of Presentation: 国立京都国際会館