Grant-in-Aid for Scientific Research (B).
|Allocation Type||Single-year Grants |
|Research Institution||Tohoku University |
NAGURA Hiroshi Department of Pathology Tohoku University Graduate Schcol of Medicine, Professor, 大学院・医学系研究科, 教授 (90022821)
KAMINOGAWA Shuichi Department of Applied Chemistry, University of Tokyo, Professor, 大学院・農学生命科学研究科, 教授 (50011945)
ISHIKAWA Hiromichi Department of Microbiology, Keio University School of Medicine, Professor, 医学部, 教授 (20051667)
KIYONO Hiroshi Department for Mucosal Immunology, Research Institute for Micorobial Diseases, Osaka University, Professor, 微生物研究所, 教授 (10271032)
YAMAKAWA Mitsunori Department of Pathology Yamagata University School of Medicine, Professor, 医学部, 教授 (20183676)
URIS Atuo Department of Pediatrics, Fujita Health University School of Medicine, Associate Professor, 医学部, 助教授 (20193972)
|Project Period (FY)
1998 – 2000
Completed(Fiscal Year 2000)
|Budget Amount *help
¥12,000,000 (Direct Cost : ¥12,000,000)
Fiscal Year 2000 : ¥3,000,000 (Direct Cost : ¥3,000,000)
Fiscal Year 1999 : ¥3,700,000 (Direct Cost : ¥3,700,000)
Fiscal Year 1998 : ¥5,300,000 (Direct Cost : ¥5,300,000)
|Keywords||mucosal immune system / food allergy / inflammatory bowel disease / oral immunization / neuroendocrine system / animal model for food allergy / intraepithelial lymphocyte / egg white allergy / 神経ペプチド / クリプトパッチ / 消化管アレルギー / 炎症性腸管障害 / 卵白アルブミン / ニューロペプチド / サイトカイン / 好中球 / CD4_+T細胞 / 消化管粘膜障害 / 炎症性粘膜障害 / 経口免疫寛容 / 粘膜ワクチン / トランスジェニックマウス|
The present investigation clarified the structural basis, regulatory mechanism and developmental process of the mucosal immune system, which play a crucial role in the mucosal defense mechanism in the gastrointestinal tract, and animal models for mucosal inflammatory diseases and food allergy were also established. These researches made a important contribution to the progress of the development in the field of the mucosal immune system, and proposed new and epoch-making ideas for treatment and prevertion of immuno-inflammatory disorders in the gastrointestinal mucosa.
1) Structure and functions of the mucosal immune system, and inflammatory and allergic intestinal disorders induced by its regulatory failure :
(1)Numerous intraepithelial T cells(IEL) bearing TCR- γδwere localized between columnar epithelial cells of the intestinal mucosa, and proved to maintain the anatomical front of the intestine under cellular maturation and constant immune surveillance. Small aggregates of ckit+Lin i
mmature lymphocytes were precusors of IEL, named by cryptpatches.
(2) Hormones and neuropeptides and their related substances such as 11β HSD and urocortin play important regulators for gastrointestinal functions including absorption of water and nutrients and mucosal defense mechanisms.
(3) Increased number of activated macrophages and lymphocytes and abundant infiltration by neutrophils indued prolonged mucosal injuries characteristics for ulcerative colitis, Crohn's disease and intestinal allergy, respectively.
2) Establishment of animal models for food allergy and elucidation of the mechanism for induction of allergy :
Systemically primed BALB/c mice and allergen-specific T cell receptor transgenic mice developed severe diarrhea after repeated oral administration of ovoalbumin.
3) Prevention and treatment of food alleregy :
(1) IgE-binding activity, to pepsin-digested ovomucoid was of diagnostic value and prediction of the out growing of egg white hypersensitivity.
(2) The animal model for food allergy showed that diatary nucleotides up-regulated the antigen-specific Th1 immune response through the enhancement of IL-12 production and suppressed the antigen specific IgE response. This implys that diatary nucleotides may be beneficial for the preventin for of allergic diseases in early infancy. Less