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2006 Fiscal Year Final Research Report Summary

Analyses of Toll-like receptors regulating innate antibody response against microbial lipids

Research Project

Project/Area Number 16390142
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionThe University of Tokyo

Principal Investigator

MIYAKE Kensuke  The University of Tokyo, Institute of Medical Science, Dep. Microbiology and Immunology, Professor, 医科学研究所, 教授 (60229812)

Project Period (FY) 2004 – 2006
Keywordsinnate immunity / endotoxin / Toll-like receptor / natural antibody
Research Abstract

Antibody responses have an important role in defense against microbial infection. Two distinct antibodies were produced during infection, innate antibodies such as IgM and IgG3 and T-dependent antibodies including IgG2a and IgG2b. The former is produced in an T-independent manner in response to lipopolysaccharides or lipopeptides. In the present study, we examined how production of innate antibodies were regulated. Radioprotective 105/MD-1 is expressed on the B cell surface and structurally related to Toll-like receptors. We previously showed that RP105 is required for B cell responses to LPS. In this project, we showed that RP105 is also required for B cell response to TLR2 ligand, lipopeptide. Moreover, serum IgG3 is specifically low in RP105 mice. To reveal a mechanism by which RP105 induces serum IgG3, we studied expression of the γ3 germline transcript, which is constitutively expressed in splenic B cells. Intrerestingly, the constitutive expression of the γ3 germline transcript was impaired in RP105^<-/-> mice. Moreover, reduced serum IgG3 was also seen in MD-1^<-/-> mice and TLR2^<-/->TLR4^<-/-> mice. These results suggest that RP105/MD-1 and TLR2/4 work in concert for inducing serum IgG3. These results suggest that B cells are responding to TLR2/4 ligands without any apparent infection. Given that TLR2/4 respoind not only to microbial ligands but also to endogenous ligands, TLR2/4 and RP105/MD-1 may have a role in B cell response to endogenous self ligands as well as to microbial ligands. IgG3 was shown to be pathogenic in lupus nephritis, we are going to study roles for TLR2/4 and RP105/MD-1 in lupus nephritis.

  • Research Products

    (8 results)

All 2006 2005

All Journal Article (8 results)

  • [Journal Article] Agonistic Antibody to Toll-like receptor 4/MD-2 Protects Mice From Acute Lethal Hepatitis Induced by Tumor Necrosis Factor-α2006

    • Author(s)
      赤司祥子
    • Journal Title

      Journal of Immunology 176

      Pages: 4244-4251

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Regulatory Roles for MD-2 and Toll-like receptor 4 (TLR4) in Ligand-induced Receptor Clustering2006

    • Author(s)
      小林真紀子
    • Journal Title

      Journal of Immunology 176

      Pages: 4244-4251

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A Protein Associated with Toll-like Receptor 4 (PRAT4A) Regulates Cell Surface Expression of TLR42006

    • Author(s)
      若林靖隆
    • Journal Title

      Journal of Immunology 177

      Pages: 1772-1779

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A molecule that is associated with Toll-like receptor 4 and regulates its cell surface expression.2006

    • Author(s)
      Konno K, et al.
    • Journal Title

      Biochem Biophys Res Commun. 339

      Pages: 1076-1082

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Agonistic Antibody to Toll-like receptor 4/MD-2 Protects Mice from Acute Lethal Hepatitis Induced by Tumor Necrosis Factor-α2006

    • Author(s)
      Akashi-Takamura S, et al.
    • Journal Title

      J.Immunol. 176

      Pages: 4244-4251

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Regulatory Roles for MD-2 and Toll-like receptor 4 (TLR4) in Ligand-induced Receptor Clustering.2006

    • Author(s)
      Kobayashi M, et al.
    • Journal Title

      J.Immunal 176

      Pages: 6211-6218

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A Protein Associated with Toll-like Receptor 4 (PRAT4A) Regulates Cell Surface Expression of TLR4.2006

    • Author(s)
      Wakabayashi Y, et al.
    • Journal Title

      J.Immunol. 177

      Pages: 1772-1779

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The Radioprotective 105/MD-1 Complex Links Toll-like Receptor 2 (TLR2) and TLR4/MD-2 in Antibody Response to Microbial Membranes2005

    • Author(s)
      Nagai Y, et al.
    • Journal Title

      J.Immunol. 174

      Pages: 7043-7049

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2008-05-27  

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