Establishment of disease mechanism of inflammatory and allergic disorders in the intestinal mucosa from the mucosal immune system and development for their treatments

本研究阐明了在胃肠道黏膜防御机制中起关键作用的黏膜免疫系统的结构基础、调节机制和发育过程，并建立了黏膜炎性疾病和食物过敏的动物模型。这些研究为粘膜免疫系统领域的发展进步做出了重要贡献，并为治疗和预防胃肠道粘膜免疫炎症性疾病提出了划时代的新思路。1）粘膜免疫系统的结构和功能，及其调控失效引起的炎症性和过敏性肠道疾病：（1）肠粘膜柱状上皮细胞之间存在大量的上皮内T细胞（intraepithelial T cell，IEL），它们在细胞成熟和持续的免疫监视下维持着肠道的解剖结构。ckit+Lin i的小聚集体 ...更多信息 未成熟淋巴细胞是IEL的前体，称为隐窝斑。(2)激素和神经肽及其相关物质如11β HSD和尿皮质素对胃肠道功能包括水和营养物质的吸收以及粘膜防御机制起着重要的调节作用。(3)激活的巨噬细胞和淋巴细胞数量的增加以及大量中性粒细胞的浸润分别诱导溃疡性结肠炎、克罗恩病和肠变态反应的持续粘膜损伤特征。2）食物变态反应动物模型的建立和变态反应诱导机制的阐明：全身致敏的BALB/c小鼠和过敏原特异性T细胞受体转基因小鼠在重复口服卵清蛋白后发生严重腹泻。3）食物过敏的预防和治疗：（1）胃蛋白酶消化卵类粘蛋白的IgE结合活性对诊断和预测卵白色过敏有一定的价值。(2)食物过敏动物模型显示，二核苷酸通过增强IL-12的产生而上调抗原特异性Th 1免疫应答，并抑制抗原特异性IgE应答。这意味着二核苷酸可能有利于预防婴儿早期过敏性疾病。少

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 … More 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