Analysis of the novel IL-27 signaling pathway involved in homeostasis of dendritic cells

• Project/Area Number: 16K19571
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: KAJITA Mihoko 東京医科歯科大学, 難治疾患研究所, 特任助教 (00607442)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: dendritic cells / WSX-1 / WSX1 / interferon gamma / 免疫学 / 樹状細胞 / IL-27

Outline of Final Research Achievements

In mice deficient for WSX-1, which is a component of IL-27 receptor, the number of dendritic cells (DCs) substantially decreased in lymphoid tissues and the mice developed systemic autoimmune diseases with age (Kajita et al. unpublished data). In this study, I found that DC development in the bone marrow culture was profoundly suppressed in aged WSX-1-deficient mice compared with young WSX-1-deficient mice. Moreover, IFN-γ treatment of bone marrow cells inhibited Flt3-induced DC development. IFN-γ treatment also suppressed Flt3 expression on the lineage negative cells in vitro. These data suggest that in aged WSX-1-deficient mice, the reduction of DCs in lymphoid tissues is caused by the aberrant development of DCs.

Research Products

• [Journal Article] The paxillin-plectin-EPLIN complex promotes apical elimination of RasV12-transformed cells by modulating HDAC6-regulated tubulin acetylation (2018)
  • Author(s): Kasai Nobuhiro、Kadeer Ailijiang、Kajita Mihoko、Saitoh Sayaka、Ishikawa Susumu、Maruyama Takeshi、Fujita Yasuyuki
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 2097-2097
  • DOI: 10.1038/s41598-018-20146-1
  • NAID: 120006456414
  • Peer Reviewed / Open Access
• [Journal Article] Intrinsic autophagy is required for the maintenance of intestinal stem cells and for irradiation-induced intestinal regeneration. (2017)
  • Author(s): Asano J, Sato T, Ichinose S, Kajita M, Onai N, Shimizu S, Ohteki T.
  • Journal Title: Cell reports Volume: 20 Issue: 5 Pages: 1050-1060
  • DOI: 10.1016/j.celrep.2017.07.019
  • Peer Reviewed / Open Access
• [Journal Article] Cell competition with normal epithelial cells promotes apical extrusion of transformed cells through metabolic changes. (2017)
  • Author(s): Shunsuke Kon, et al.
  • Journal Title: Nature Cell Biology Volume: 印刷中 Issue: 5 Pages: 530-541
  • DOI: 10.1038/ncb3509
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Plectin is a novel regulator for apical extrusion of RasV12-transformed cells. (2017)
  • Author(s): Kadeer, A., Maruyama, T., Kajita, M., Morita T., Sasaki, A., Ohoka, A., Ishikawa, S., Ikegawa, M., Shimada, T., and Fujita, Y.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 44328-44328
  • DOI: 10.1038/srep44328
  • NAID: 120006219881
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Rab5-regulated endocytosis plays a crucial role in apical extrusion of transformed cells. (2017)
  • Author(s): S. Saitoh, T. Maruyama, Y. Yako, M. Kajita, Y. Fujioka, Y. Ohba, N. Kasai, N. Sugama, S. Kon, S. Ishikawa, T. Hayashi, T. Yamazaki, M. Tada and Y. Fujita.
  • Journal Title: Proc. Natl. Acad. Sci. U.S.A. Volume: 114 Issue: 12
  • DOI: 10.1073/pnas.1602349114
  • NAID: 120006346108
  • Peer Reviewed / Open Access / Int'l Joint Research