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2009 Fiscal Year Annual Research Report

リンパ球表面分子および細胞内シグナル伝達分子を標的とした免疫アレルギー疾患の制御

Research Project

Project/Area Number 20390282
Research InstitutionJuntendo University

Principal Investigator

奥村 康  Juntendo University, 医学部, 特任教授 (50009700)

Co-Investigator(Kenkyū-buntansha) 中野 裕康  順天堂大学, 医学部, 准教授 (70276476)
秋葉 久弥  順天堂大学, 医学部, 准教授 (60338316)
牛尾 博子  順天堂大学, 医学部, 准教授 (30317391)
Keywordsマスト細胞 / オートファジー / インターフェロン / Liht chain(LC)3 / ノックアウトマウス / 脱顆粒 / IgE / CD63
Research Abstract

マスト細胞でオートファジーが恒常的に誘導されているかを検討するために、野生型マウス骨髄より誘導したマスト細胞を用いて検討したところ、オートファジー誘導マーカーの一つであるlight chain(LC)3のII型が強く発現していること、および共焦点顕微鏡を用いた免疫染色でもLC3がdotを形成していることを見いだした。atg7-/-マウスは生後1目以内に飢餓応答がうまくいかずに死亡してしまう。そこでatg7^<flox/flox>マウスとI型インターフェロンによりCreリコンビネースの発現を誘導できるMX1-Creマウスを交配し、atg7^<flox/flox>:Mx1-Creマウスを作成した。このマウスの腹腔にpolyICを注射することにより、骨髄細胞からatg7を欠損させ、骨髄細胞よりマスト細胞を誘導して解析したところ、マスト細胞の分化誘導には障害が認められなかった。しかし、免疫電顕を用いた解析からLC3がマスト細胞の穎粒内に認められたことから、IgE受容体の架橋による脱顆粒をbeta-hexoaminidaseやヒスタミンの細胞外放出を指標に検討したところ、野生型マウスに比較してatg7-/-マスト細胞で脱顆粒が有意に低下していることが明らかとなった。さらにマスト細胞の脱顆粒に伴いsecretory lysosomeマーカーであるCD63やオートファゴソーム膜上に存在すると考えられるLC3のII型も細胞外に放出されることを明らかにした。一方atg7-/-マスト細胞はIgE刺激に伴うIL-6などの炎症性サイトカインの産生や、MAPキナーゼ系のリン酸化には障害が認められなかった。以上よりマスト細胞では恒常的にオートファジーが誘導されていること、抗原刺激によるマスト細胞の脱顆粒にはオートファジーが重要な役割を果たしていることが明らかとなった。

  • Research Products

    (43 results)

All 2010 2009

All Journal Article (40 results) (of which Peer Reviewed: 40 results) Presentation (3 results)

  • [Journal Article] Synergistic augmentation of inflammatory cytokine productions from murine mast cells by monomeric IgE and toll-like receptor ligands2010

    • Author(s)
      Takenaka, H., et al.
    • Journal Title

      Biochem Biophys Res Commun 391

      Pages: 471-476

    • Peer Reviewed
  • [Journal Article] Tissue type plasminogen activator regulates myeloid-cell dependent neoangiogenesis during tissue regeneration2010

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

      Blood (In press)

    • Peer Reviewed
  • [Journal Article] Antimicrobial Peptides Human{beta}-Defensins and Cathelicidin LL-37 Induce the Secretion of a Pruritogenic Cytokine IL-31 by Human Mast Cells2010

    • Author(s)
      Niyonsaba, F., et al.
    • Journal Title

      J Immunol (In press)

    • Peer Reviewed
  • [Journal Article] FcepsilonRIalpha gene(FCER1A)promoter polymorphisms and total serum IgE levels in Japanese atopic dermatitis patients2010

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

      Int J Immunogenet (In press)

    • Peer Reviewed
  • [Journal Article] Staphylococcus aureus extracellular protease causes epidermal barrier dysfunction2010

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

      J Invest Dermatol 130

      Pages: 614-617

    • Peer Reviewed
  • [Journal Article] Contribution of B7RP-1/ICOS co-stimulation to lethal acute GVHD2010

    • Author(s)
      Fujimura, J., et al.
    • Journal Title

      Pediatr Transplant (In press)

    • Peer Reviewed
  • [Journal Article] NADPH oxidase activity in allergenic pollen grains of different plant species2009

    • Author(s)
      Wang, X.L., et al.
    • Journal Title

      Biochem Biophys Res Commun 387

      Pages: 430-434

    • Peer Reviewed
  • [Journal Article] Suppression of experimental autoimmune uveoretinitis by regulatory dendritic cells in mice2009

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

      Arch Ophthalmol 127

      Pages: 514-519

    • Peer Reviewed
  • [Journal Article] RANK-RANKL signaling pathway is critically involved in the function of CD4+CD25+ regulatory T cells in chronic colitis2009

    • Author(s)
      Totsuka, T., et al.
    • Journal Title

      J Immunol 182

      Pages: 6079-6087

    • Peer Reviewed
  • [Journal Article] Enzyme-Linked Immunosorbent Assays with High Sensitivity for Antigen-Specific and Total Murine IgE : A Useful Tool for the Study of Allergies in Mouse Models2009

    • Author(s)
      Takai, T., et al.
    • Journal Title

      Allergol Int 58

      Pages: 225-235

    • Peer Reviewed
  • [Journal Article] Modulation of allergenicity of major house dust mite allergens Der f1 and Derp 1 by interaction with an endogenous ligand2009

    • Author(s)
      Takai, T., et al.
    • Journal Title

      J Immunol 183

      Pages: 7958-7965

    • Peer Reviewed
  • [Journal Article] Development of transgenic rice expressing mite antigen for a new concept of immunotherapy2009

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

      Int Arch Allergy Immunol 149

      Pages: 21-24

    • Peer Reviewed
  • [Journal Article] Activation of tumour-necrosis factor-related apoptosis-inducing ligand receptor enhances the severity of murine allergic conjunctivitis2009

    • Author(s)
      Sumi, T., et al.
    • Journal Title

      Br J Ophthalmol 93

      Pages: 110-115

    • Peer Reviewed
  • [Journal Article] Functional analysis of a polymorphism in the promoter region of the IL-12/23p40 gene2009

    • Author(s)
      Shimokawa, N., et al.
    • Journal Title

      Clin Exp Allergy 39

      Pages: 228-235

    • Peer Reviewed
  • [Journal Article] SLPI prevents cytokine release in mite protease-exposed conjunctival epithelial cells2009

    • Author(s)
      Seto, T., et al.
    • Journal Title

      Biochem Biophys Res Commun 379

      Pages: 681-685

    • Peer Reviewed
  • [Journal Article] Differential regulation of splenic CD8-dendritic cells and marginal zone B cells by Notch ligands2009

    • Author(s)
      Sekine, C., et al.
    • Journal Title

      Int Immunol 21

      Pages: 295-301

    • Peer Reviewed
  • [Journal Article] Interaction of functional FCER2 promoter polymorphism and phenotype-associated haplotypes2009

    • Author(s)
      Potaczek, D.P., et al.
    • Journal Title

      Tissue Antigens 74

      Pages: 534-538

    • Peer Reviewed
  • [Journal Article] FcepsilonRIalpha gene -18483A>C polymorphism affects transcriptional activity through YY1 binding2009

    • Author(s)
      Potaczek, D.P., et al.
    • Journal Title

      Immunogenetics 61

      Pages: 649-655

    • Peer Reviewed
  • [Journal Article] Treatment with anti-FasL antibody preserves memory lymphocytes and virus-specific cellular immunity in macaques challenged with simian immunodeficiency virus2009

    • Author(s)
      Poonia, B., at al.
    • Journal Title

      Blood 114

      Pages: 1196-1204

    • Peer Reviewed
  • [Journal Article] The human antimicrobial peptide dermcidin activates normal human keratinocytes2009

    • Author(s)
      Niyonsaba, F., et al.
    • Journal Title

      Br J Dermatol 160

      Pages: 243-249

    • Peer Reviewed
  • [Journal Article] Multifunctional antimicrobial proteins and peptides : natural activators of immune systems2009

    • Author(s)
      Niyonsaba, F., et al.
    • Journal Title

      Curr Pharm Des 15

      Pages: 2393-2413

    • Peer Reviewed
  • [Journal Article] Human umbilical cord epithelial cells express Notch ligands Delta1 and Jagged12009

    • Author(s)
      Ng, W., et al.
    • Journal Title

      J Dermatol Sci 54

      Pages: 131-134

    • Peer Reviewed
  • [Journal Article] Tim-3 mediates phagocytosis of apoptotic cells and cross-presentation2009

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

      Blood 113

      Pages: 3821-3830

    • Peer Reviewed
  • [Journal Article] Notch signaling confers antigen-presenting cell functions on mast cells2009

    • Author(s)
      Nakano, N., et al.
    • Journal Title

      J Allergy Clin Immunol 123

      Pages: 74-81

    • Peer Reviewed
  • [Journal Article] House dust mite allergen Der f 1 can induce the activation of latent TGF-beta via its protease activity2009

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

      FEBS Lett 583

      Pages: 2088-2092

    • Peer Reviewed
  • [Journal Article] The latent form of transforming growth factor-beta administered orally is activated by gastric acid in mice2009

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

      J Nutr 139

      Pages: 1463-1468

    • Peer Reviewed
  • [Journal Article] Thymic stromal lymphopoietin is a critical mediator of IL-13-driven allergic inflammation2009

    • Author(s)
      Miyata, M.
    • Journal Title

      Eur J Immunol 39

      Pages: 3078-3083

    • Peer Reviewed
  • [Journal Article] Inhibition of double-stranded RNA-induced TSLP in human keratinocytes by glucocorticoids2009

    • Author(s)
      Le, T.A., et al.
    • Journal Title

      Allergy 64

      Pages: 1231-1232

    • Peer Reviewed
  • [Journal Article] Cytokine milieu modulates release of thymic stromal lymphopoietin from human keratinocytes stimulated with double-stranded RNA2009

    • Author(s)
      Kinoshita, H., et al.
    • Journal Title

      J Allergy Clin Immunol 123

      Pages: 179-186

    • Peer Reviewed
  • [Journal Article] NKG2A inhibits invariant NKT cell activation in hepatic injury2009

    • Author(s)
      Kawamura, T., et al.
    • Journal Title

      J Immunol 182

      Pages: 250-258

    • Peer Reviewed
  • [Journal Article] Mite serine protease activates protease -activated receptor-2 and induces cytokine release in human keratinocytes2009

    • Author(s)
      Kato, T., et al.
    • Journal Title

      Allergy 64

      Pages: 1366-1374

    • Peer Reviewed
  • [Journal Article] Cupressaceae pollen grains modulate dendritic cell response and exhibit IgE-inducing adjuvant activity in vivo2009

    • Author(s)
      Kamijo, S., et al.
    • Journal Title

      J Immunol 183

      Pages: 6087-6094

    • Peer Reviewed
  • [Journal Article] Roles of PU.1 in monocyte- and mast cell-specific gene regulation : PU.1 transactivates CIITA pIV in cooperation with IFN-gamma2009

    • Author(s)
      Ito, T., et al.
    • Journal Title

      Int Immunol 21

      Pages: 803-816

    • Peer Reviewed
  • [Journal Article] Lipid-soluble components of honeybee-collected pollen exert antiallergic effect by inhibiting IgE-mediated mast cell activation in vivo2009

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

      Phytother Res 23

      Pages: 1581-1586

    • Peer Reviewed
  • [Journal Article] Lipopolysaccharide binding of the mite allergen Derf22009

    • Author(s)
      Ichikawa, S., et al.
    • Journal Title

      Genes Cells 14

      Pages: 1055-1065

    • Peer Reviewed
  • [Journal Article] Involvement of PU.1 in the transcriptional regulation of TNF-alpha2009

    • Author(s)
      Fukai, T., et al.
    • Journal Title

      Biochem Biophys Res Commun 388

      Pages: 102-106

    • Peer Reviewed
  • [Journal Article] Anti-tumor immunity in a model of acute myeloid leukemia2009

    • Author(s)
      Cheuk, A.T., et al.
    • Journal Title

      Leuk Lymphoma 50

      Pages: 447-454

    • Peer Reviewed
  • [Journal Article] NF-κB2(p100)limits TNF-alpha-induced osteoclastogenesis2009

    • Author(s)
      Tanaka, S., Nakano, H.
    • Journal Title

      J Clin Invest 119

      Pages: 2879-2881

    • Peer Reviewed
  • [Journal Article] TRAF5 is a critical mediator of in vitro signals and in vivo functions of LMP1, the viral oncogenic mimic of CD402009

    • Author(s)
      Kraus, Z.J., Nakano, H., Bishop, G.A.
    • Journal Title

      Proc Natl Acad Sci USA 106

      Pages: 17140-17145

    • Peer Reviewed
  • [Journal Article] TRAF2 phosphorylation modulates tumor necrosis factor α-induced gene expression and cell resistance to apoptosis2009

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

      Mol Cell Biol 29

      Pages: 303-314

    • Peer Reviewed
  • [Presentation] A crucial role for constitutive autophagy in degranulation of mast cells2009

    • Author(s)
      Ushio, et al.
    • Organizer
      第39回日本免疫学会総会
    • Place of Presentation
      大阪
    • Year and Date
      20091202-20091204
  • [Presentation] Spontaneous development of severe inflammatory bowel disease in traf2-/-mice2009

    • Author(s)
      Piao, et al.
    • Organizer
      第39回日本免疫学会総会
    • Place of Presentation
      大阪
    • Year and Date
      20091202-20091204
  • [Presentation] Downregulation of c-FLIP promotes caspase-dependent ROS and JNK activation in tumor cells2009

    • Author(s)
      Nakano, et al.
    • Organizer
      12 th International TNF conference
    • Place of Presentation
      Madrid, Spain
    • Year and Date
      20090426-20090429

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Published: 2011-06-16   Modified: 2016-04-21  

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