Role of MAP3Ks in the maintenance of mucosal immune homeostasis

• Project/Area Number: 21790460
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: The University of Tokyo
• Principal Investigator: SATO Shintaro The University of Tokyo, 医科学研究所, 助教 (80447333)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 粘膜免疫 / 腸管上皮細胞 / MAP3K / 遺伝子改変マウス / MAP3K3 / MEKK3 / 炎症性腸疾患 / ノックアウトマウス

Research Abstract

MAP3K family members act at upstream of MAPK such as JNK and p38. Among them, it has been reported that TAK1 and MEKK3 are also involved in the activation of NF-κB in response to several stimuli. We made conditional TAK1-deficient mice including intestinal epithelial cell-specific one (TAK1^<IEC-KO>), and reported the role of TAK1 in vivo. In this study, to elucidate the in vivo role of MEKK3 at IEC, we made and analyzed MEKK3^<IEC-KO> mice, and compared them with TAK1^<IEC-KO> mice. As a result, it was revealed that MEKK3, but not TAK1, was not involved in the activation of NF-κB in IEC. In addition, it was suggested that MEKK3 participated in maintenance of homeostasis of IEC.

Research Products

• [Journal Article] Inflammatory Mediator TAK1 Regulates Hair Follicle Morphogenesis and Anagen Induction Shown by Using Keratinocyte-Specific TAK1-Deficient Mice. (2010)
  • Author(s): Sayama K, Kajiya K, Sugawara K, Sato S, Hirakawa S, Shirakata Y, Hanakawa Y, Dai X, Ishimatsu-Tsuji Y, Metzger D, Chambon P, Akira S, Paus R, Kishimoto J, Hashimoto K.
  • Journal Title: PLoS ONE. 5
• [Journal Article] Indigenous opportunistic bacteria inhabit mammalian gut-associated lymphoid tissues and share a mucosal antibody-mediated symbiosis. (2010)
  • Author(s): Obata T, Goto Y, Kunisawa J, Sato S, Sakamoto M, Setoyama H, Matsuki T, Nonaka K, Shibata N, Gohda M, Kagiyama Y, Nochi T, Yuki Y, Fukuyama Y, Mukai A, Shinzaki S, Fujihashi K, Sasakawa C, Iijima H, Goto M, Umesaki Y, Benno Y, Kiyono H.
  • Journal Title: Proc Natl Acad Sci USA. 107 Pages: 7419-7424
• [Journal Article] Intracellular Mycobacterium avium Intersect Transferrin in the Rab11(+) Recycling Endocytic Pathway and Avoid Lipocalin 2 Trafficking to the Lysosomal Pathway. (2010)
  • Author(s): Halaas O, Steigedal M, Haug M, Awuh JA, Ryan L, Brech A, Sato S, Husebye H, Cangelosi GA, Akira S, Strong RK, Espevik T, Flo TH.
  • Journal Title: J Infect Dis. 201 Pages: 783-792
• [Journal Article] LGP2 is a positive regulator of RIG-I-and MDA5-mediated antiviral responses. (2010)
  • Author(s): Satoh T, Kato H, Kumagai Y, Yoneyama M, Sato S, Matsushita K, Tsujimura T, Fujita T, Akira S, Takeuchi O.
  • Journal Title: Proc Natl Acad Sci USA. 107 Pages: 1512-1517
• [Journal Article] Indigenous opportunistic bacteria inhabit mammalian gut-associated lymphoid tissues and share a mucosal antibody-mediated symbiosis. (2010)
  • Author(s): Obata, T., et al.
  • Journal Title: Proc.Natl.Acad.Sci.USA. Volume: 107 Pages: 7419-7424
  • Peer Reviewed
• [Journal Article] Inflammatory Mediator TAK1 Regulates Hair Follicle Morphogenesis and Anagen Induction Shown by Using Keratinocyte-Specific TAK1-Deficient Mice. (2010)
  • Author(s): Sayama, K., et al.
  • Journal Title: PLoS ONE Volume: 5
  • Peer Reviewed
• [Journal Article] LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses (2010)
  • Author(s): Satoh, T., et al.
  • Journal Title: Proc.Natl.Acad.Sci.USA. 107 Pages: 1512-1517
  • Peer Reviewed
• [Journal Article] Intracellular Mycobacterium avium Intersect Transferrin in the Rabll(+) Recycling Endocytic Pathway and Avoid Lipocalin 2 Trafficking to the Lysosomal Pathway (2010)
  • Author(s): Halaas, O., et al.
  • Journal Title: J.Infect.Dis. 201 Pages: 783-792
  • Peer Reviewed
• [Journal Article] Id2-, RORγt-, and LTβR-independent initiation of lymphoid organogenesis in ocular immunity. (2009)
  • Author(s): Nagatake T, Fukuyama S, Kim DY, Goda K, Igarashi O, Sato S, Nochi T, Sagara H, Yokota Y, Jetten AM, Kaisho T, Akira S, Mimuro H, Sasakawa C, Fukui Y, Fujihashi K, Akiyama T, Inoue J, Penninger JM, Kunisawa J, Kiyono H.
  • Journal Title: J Exp Med. 206 Pages: 2351-2364
• [Journal Article] Rasschaert J. Regulation and function of the cytosolic viral RNA sensor RIG-I in pancreatic beta cells. (2009)
  • Author(s): Garcia M, Dogusan Z, Moore F, Sato S, Hartmann G, Eizirik DL
  • Journal Title: Biochim Biophys Acta. 1793 Pages: 1768-1775
• [Journal Article] Regulation and function of the cytosolic viral RNA sensor RIG-1 in pancreatic beta cells (2009)
  • Author(s): Garcia, M., et al.
  • Journal Title: Biochim.Biophys.Acta. 1793 Pages: 1768-1775
  • Peer Reviewed
• [Journal Article] Id2-,RORγt-, LTβR-independent initiation of lymphoid organogenesis in ocular immunity (2009)
  • Author(s): Nagatake, T., et al.
  • Journal Title: J.Exp.Med. 206 Pages: 2351-2364
  • Peer Reviewed
• [Remarks] ホームページ等
• [Patent(Industrial Property Rights)] 炎症性腸疾患の検査方法及び検査用キット (2010)
  • Inventor(s): 清野宏、佐藤慎太郎、小幡高士、飯島英樹
  • Industrial Property Rights Holder: 清野宏、佐藤慎太郎、小幡高士、飯島英樹
  • Filing Date: 2010-03-26
• [Patent(Industrial Property Rights)] 炎症性腸疾患の検査方法及び検査用キット (2010)
  • Inventor(s): 清野宏, 佐藤慎太郎, 小幡高士, 飯島英樹
  • Industrial Property Rights Holder: 清野宏, 佐藤慎太郎, 小幡高士, 飯島英樹
  • Industrial Property Number: 2010-072790
  • Filing Date: 2010-03-26