Induction of oral tolerance by plasmacytoid dendritic cells in the intestinal lamina propria

• Project/Area Number: 16590399
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: The University of Tokyo
• Principal Investigator: HIROI Takachika The University of Tokyo, The Institute of Medical Science, Department of Mucosal Immunology, Research Associate, 医科学研究所, 助手 (80228824)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥2,500,000 (Direct Cost: ¥2,500,000); Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
• Keywords: Mucosal immunology / Intestinal lamina propria / Oral tolerance / Eosinophil / Dendritic cells / Regulatory T cells / TGF-β / IgA / MHC-class II / TGF-b

Research Abstract

We have identified a novel subset of eosinophils in the intestinal lamina propria which are capable of expressing morphological and functional characteristics of dendritic cells. These eosinophils, which express Gr-1^+CD11c^+F4/80^+CD11b^+B220^- surface phenotypic markers, can initiate inhibition from their site of residence and so play a pivotal role in the induction of oral tolerance that is independent of CD4^+CD25^+ T regulatory cell-mediated inhibitory effects. When activated with CpG/Flt3-L, intestinal eosinophils acquire typical dendritic morphology and confer an antigen-specific T cell unresponsiveness that is dependent on their low expression of co-stimulatory molecules and increased production of TGF-β.

Research Products

• [Journal Article] CCR7 is critically important for migration of immunomodulatory dendritic cells in intestinal lamina propria to mesenteric lymph nodes. (2006)
  • Author(s): Jang, MH., et al.
  • Journal Title: Journal of Immunology 176 Pages: 803-810
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Differences in integrin-dependent phagocytosis among three hemocyte subpopulations of the Pacific oyster "Crassostrea gigas" (2006)
  • Author(s): Terahara, K., et al.
  • Journal Title: Dev. Comp. Immunol. 30 Pages: 667-683
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 腸管系樹状細胞の特性とその生物学的機能 (2005)
  • Author(s): 廣井隆親 他
  • Journal Title: BIO Clinica 20 Pages: 43-49
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Colitis in mice lacking the common cytokine receptor gamma chain is mediated by IL-6-producing CD4^+ T cells. (2005)
  • Author(s): Kai, Y., et al.
  • Journal Title: Gastroenterology 128 Pages: 922-934
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A rice-based edible vaccine expressing multiple T cell epitopes induces oral tolerance for inhibition of Th2-mediated IgE responses. (2005)
  • Author(s): Takagi, H., et al.
  • Journal Title: Proc. Natl. Acad. Sci. USA. 102 Pages: 17525-17530
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Prenatal blockage of lymphotoxin {beta} receptor and TNF receptor p55 signaling cascade resulted in the acceleration of tissue genesis for isolated lymphoid follicles in the large intestine. (2005)
  • Author(s): Kweon, M.N., et al.
  • Journal Title: Journal of Immunology 174 Pages: 4365-4372
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 経口免疫寛容における粘膜固有層樹状細胞の役割 (2005)
  • Author(s): 廣井隆親 他
  • Journal Title: 臨床免疫 44 Pages: 104-108
  • NAID: 40006859397
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 粘膜免疫におけるIgAクラススイッチ (2005)
  • Author(s): 廣井隆親 他
  • Journal Title: 免疫2006 42 Pages: 342-351
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Recent advances in Otitis media (2005)
  • Author(s): Fukuyama, S., et al.
  • Journal Title: BC Decker, Lewiston, NY
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A rice-based edible vaccine expressing multiple T cell epitopes induces oral tolerance for inhibition of Th2-mediated IgE responses. (2005)
  • Author(s): Takagi, H., et al.
  • Journal Title: Proc.Natl.Acad.Sci.USA. 102 Pages: 17525-17530
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Induction of oral tolerance by antigen presenting cells in the intestinal lamina propria (2005)
  • Author(s): Hiroi, T. et al.
  • Journal Title: Clinical Immunology (Japanese) 44 Pages: 104-108
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] IgA class switch in mucosal immunology (2005)
  • Author(s): Hiroi, T. et al.
  • Journal Title: Immunology 2006 (Japanese) 42 Pages: 342-351
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] CCR7 is critically important for migration of immunomodulatory dendritic cells in intestinal lamina propria to mesenteric lymph nodes. (2005)
  • Author(s): Jang, MH, et al.
  • Journal Title: Journal of Immunology 176 Pages: 803-810
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Differences in integrin-dependent phagocytosis among three hemocyte subpopulations of the Pacific oyster "Crassostrea gigas" (2005)
  • Author(s): Terahara, K., et al.
  • Journal Title: Dev.Comp.Immunol. 30 Pages: 667-683
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Prenatal Blockage of Lymphotoxin {beta} Receptor and TNF Receptor p55 Signaling Cascade Resulted in the Acceleration of Tissue Genesis for Isolated Lymphoid Follicles in the Large Intestine. (2005)
  • Author(s): Kweon, M.N., Hiroi, T., et al.
  • Journal Title: Journal of immunology 174 Pages: 4365-4372
• [Journal Article] Colitis in mice lacking the common cytokine receptor gamma chain is mediated by IL-6-producing CD4^+ T cells. (2005)
  • Author(s): Kai, Y., Hiroi, T., et al.
  • Journal Title: Gastroenterology 128 Pages: 922-934
• [Journal Article] A rice-based edible vaccine expressing multiple T cell epitopes induces oral tolerance for inhibition of Th2-mediated IgE responses. (2005)
  • Author(s): Takagi, H., Hiroi, T., et al.
  • Journal Title: Proc.Natl.Acad.Sci.USA. 102 Pages: 17525-17530
• [Journal Article] CCR7 is critically important for migration of immunomodulatory dendritic cells in intestinal lamina propria to mesenteric lymph nodes. (2005)
  • Author(s): Jang, M.H., Hiroi, T., et al.
  • Journal Title: Journal of immunology 印刷中
• [Journal Article] 腸管系樹状細胞の特性とその生物学的機能 (2005)
  • Author(s): 廣井隆親, 他
  • Journal Title: BIO Clinica 20 Pages: 43-49
• [Journal Article] 経口免疫寛容における粘膜固有層樹状細胞の役割 (2005)
  • Author(s): 廣井隆親, 他
  • Journal Title: 臨床免疫 44 Pages: 104-108
  • NAID: 40006859397
• [Journal Article] 粘膜免疫におけるIgAクラススイッチ (2005)
  • Author(s): 廣井隆親, 他
  • Journal Title: 免疫2006 42 Pages: 342-351
• [Journal Article] Differences in integrin-dependent phagocytosis among three hemocyte subpopulation of the Pacific oyster Crassostrea gigas. (2005)
  • Author(s): Terahara, K., Hiroi, T., et al.
  • Journal Title: Dev.Comp.Immunol. 印刷中
• [Journal Article] Absence of common cytokine receptor γ chain results in the development of colitis by IL-6-producing pathogenic CD4^+ T cells crγ^<-/Y> mice. (2005)
  • Author(s): Kai, Y., Takahashi, I., Ishikawa, H., Hiroi, T., Mizushima, T., Kishi, D., Hamada, H., Tamagawa, H., Ito, T., Yoshizaki, K., Kishimoto, T., Matsuda, H., Kiyono, H.
  • Journal Title: Gastroentelogy (印刷中)
• [Journal Article] Prenatal blockage of LTβR and TNFRp55 signaling cascade resulted in the acceleration of tissue genesis for isolated lymphoid follicles in the large intestine. (2005)
  • Author(s): Kweon, M.N., Yamamoto, M., Rennert, P.D., Park, E.J., Hiroi, T., Kiyono, H.
  • Journal Title: Journal of Immunology (印刷中)
• [Journal Article] IgA isotype class switching occurs in the organized mucosal lymphoid tissue, but not in the diffused lamina propria of nasal and intestinal tissues. (2004)
  • Author(s): Shikina, T. et al.
  • Journal Title: Journal of Immunology 172 Pages: 6259-6264
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Intestinal villous M cells : An antigen entry site in the mucosal epithelium. (2004)
  • Author(s): Jang, M-N., et al.
  • Journal Title: Proc. Natl. Acad. Sci. USA. 93 Pages: 3613-3618
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Role of gut-associated lymphoreticular tissues in antigen-specific intestinal IgA immunity. (2004)
  • Author(s): Yamamoto, M., et al.
  • Journal Title: Journal of Immunology 173 Pages: 762-769
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Intracellularly Expressed TLR2s and TLR4s Contribution to an Immuno-Silent Environment at the Ocular Mucosal Epithelium. (2004)
  • Author(s): Ueta, M., et al.
  • Journal Title: Journal of Immunology 173 Pages: 3337-3347
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 口腔内疾患と粘膜ワクチン (2004)
  • Author(s): 廣井隆親 他
  • Journal Title: アニテックス 16 Pages: 102-116
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Intestinal villous M cells : An antigen entry site in the mucosal epithelium. (2004)
  • Author(s): Jang, M-N., et al.
  • Journal Title: Proc.Natl.Acad.Sci.USA. 93 Pages: 3613-3618
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Role of Gut Associated Lymphoreticular Tissues in Antigen-Specific Intestinal IgA Immunity. (2004)
  • Author(s): Yamamoto, M., et al.
  • Journal Title: Journal of Immunology 173 Pages: 762-769
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Role of gut-associated lymphoreticular tissues in antigen-specific intestinal IgA immunity. (2004)
  • Author(s): Ueta, M., et al.
  • Journal Title: Journal of Immunology 173 Pages: 3337-3347
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Oral disease and mucosal vaccine (2004)
  • Author(s): Hiroi, T. et al.
  • Journal Title: Anitex. (Japanese) 16 Pages: 102-116
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Biological functions of intestinal dendritic cells (2004)
  • Author(s): Hiroi, T. et al.
  • Journal Title: BIO Clinica. 20 Pages: 43-49
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] IgA isotype class switching occurs in the organized mucosal lymphoid tissue, but not in the diffused lamina propria of nasal and intestinal tissues. (2004)
  • Author(s): Shikina, T., Hiroi, T., Iwatani, K., Jang M-N., Fukuyama, S., Tamura, M., Kubo, T., Ishikawa, H., Kiyono, H.
  • Journal Title: Journal of Immunology 172 Pages: 6259-6264
• [Journal Article] Intestinal villous M cells : An antigen entry site in the mucosal epithelium. (2004)
  • Author(s): Jang, M-N., Kweon, M-N., Iwatani, K., Yamamoto, M., Terahara, K., Sasakawa, C., Suzuki, T., Nochi, T., Yokota, Y., Rennert, P.D., Hiroi, T., Tamagawa, H., Iijima, H., Kunisawa, J., Yuki, Y., Kiyono, H.
  • Journal Title: Proc.Natl.Acad.Sci.USA. 93 Pages: 3613-3618
• [Journal Article] Role of Gut-Associated Lymphoreticular Tissues in Antigen-Specific Intestinal IgA Immunity. (2004)
  • Author(s): Yamamoto, M., Kweon, M.N., Rennert, P.D., Hiroi, T., Fujihashi, K., McGhee, J.R., Kiyono, H.
  • Journal Title: Journal of Immunology 173 Pages: 762-769
• [Journal Article] Intracellularly Expressed TLR2s and TLR4s Contribution to an Immuno-Silent Environment at the Ocular Mucosal Epithelium. (2004)
  • Author(s): Ueta, M., Nochi, T., Jang, M-H., Kawasaki, S., Park, E-J., Igarashi, O., Hino, A., Kawasaki, S., Shikina, T., Hiroi, T., Kinoshita, S., Kiyono, H.
  • Journal Title: Journal of Immunology 173 Pages: 3337-3347
• [Book] Recent advances in Otitis media (2005)
  • Author(s): Fukuyama, S., et al.
  • Total Pages: 150
  • Publisher: BC Decker, Lewiston, NY
  • Description: 「研究成果報告書概要(和文)」より
• [Book] Recent advances in Otitis media (2005)
  • Author(s): Fukuyama, S., Hiroi, T., et al.
  • Total Pages: 150
  • Publisher: BC Decker, Lewiston, NY