Analysis of IL-7 niche in bone marrow

• Project/Area Number: 26860322
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Kyoto University
• Principal Investigator: Hara Takahiro 京都大学, ウイルス研究所, 助教 (90512301)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 骨髄 / ストローマ細胞 / IL-7

Outline of Final Research Achievements

Hematopoietic stem cells (HSCs) give rise to all types of blood cells including B lymphocytes. HSCs self-renew in bone marrow niches formed by CAR cells and sinusoidal endothelial cells. It has been predicted that interleukin-7 (IL-7)-dependent B lymphopoiesis is supported by osteoblasts in endosteal region, because in vitro differentiated osteoblasts have the potential to produce IL-7. However, very little is understood about the identity of IL-7-expressing cells in vivo. Here, we show that IL-7-expressing cells form a large subset of CAR cells. Conditional IL-7 deletion in CAR cells dramatically reduced pro B cells and pre B cells, whereas IL-7 deletion in osteoblasts has no effect on B lymphopoiesis. Our studies demonstrate that HSC maintenance and B cell lineage differentiation are distinct cell lineage decisions controlled by HSC niches.

Research Products

• [Int'l Joint Research] Yale University School of Medicine(米国)
• [Journal Article] STAT5 Orchestrates Local Epigenetic Changes for Chromatin Accessibility and Rearrangements by Direct Binding to the TCRγ Locus. (2015)
  • Author(s): Wagatsuma K, Tani-Ichi S, Liang B, Shitara S, Ishihara K, Abe M, Miyachi H, Kitano S, Hara T, Nanno M, Ishikawa H, Sakimura K, Nakao M, Kimura H, Ikuta K.
  • Journal Title: J Immunol. Volume: 195 Issue: 4 Pages: 1804-14
  • DOI: 10.4049/jimmunol.1302456
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] An Enhancer of the IL-7 Receptor α-Chain Locus Controls IL-7 Receptor Expression and Maintenance of Peripheral T Cells. (2015)
  • Author(s): Abe A, Tani-ichi S, Shitara S, Cui G, Yamada H, Miyachi H, Kitano S, Hara T, Abe R, Yoshikai Y, Ikuta K.
  • Journal Title: J. Immunol. Volume: 195 Issue: 7 Pages: 3129-3138
  • DOI: 10.4049/jimmunol.1302447
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Characterization of the interleukin-15 niche in primary and secondary lymphoid organs in vivo. (2014)
  • Author(s): Cui G, Hara T, Simmons S, Wagatsuma K, Abe A, Miyachi H, Kitano S, Ishii M, Tani-ichi S, Ikuta K.
  • Journal Title: Proc Natl Acad Sci USA Volume: 111 Issue: 5 Pages: 1915-1920
  • DOI: 10.1073/pnas.1318281111
  • Peer Reviewed
• [Journal Article] Environments of B cell development (2014)
  • Author(s): Tsuneto M, Kajikhina E, Seiler K, Reimer A, Tornack J, Bouquet C, Simmons S, Knoll M, Wolf I, Tokoyoda K, Hauser A, Hara T, Tani-ichi S, Ikuta K, Grün JR, Grützkau A, Engels N, Wienands J, Yanagisawa Y, Ohnishi K, Melchers F.
  • Journal Title: Immunology and Cell Biology Volume: 160 Issue: 2 Pages: 109-112
  • DOI: 10.1016/j.imlet.2014.05.005
  • Peer Reviewed
• [Presentation] Identification and characterization of IL-7 niche in gut-associated lymphoid tissues (2015)
  • Author(s): HARA Takahiro, IKUTA Kooichi
  • Organizer: 第44回 日本免疫学会総会・学術集会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2015-11-19
• [Presentation] Identification of IL-7 and IL-15 niche in lymphoid organs (2015)
  • Author(s): HARA Takahiro
  • Organizer: The 56th Annual Meeting and International Symposium of Korean Society of Life Science
  • Place of Presentation: 韓国、changwon convention center
  • Year and Date: 2015-08-27
  • Invited
• [Presentation] Distribution and function of IL-7- and IL-15-expressing cells in intestines (2014)
  • Author(s): HARA Takahiro, CUI Guangwei, IKUTA Koichi
  • Organizer: 日本免疫学会総会・学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-12-12
• [Remarks] 京都大学ウイルス研究所
  • URL: http://www.virus.kyoto-u.ac.jp/
• [Remarks] 京都大学 ウイルス研究所 生体防御研究分野
  • URL: http://www.virus.kyoto-u.ac.jp/Lab/ikutalab/ikuta.html
• [Remarks] 京都大学ウイルス研究所 生体防御研究分野
  • URL: http://www.virus.kyoto-u.ac.jp/Lab/ikuta.html