The MUC2 Mucus Gel as an Innate Immune Mechanism that Inhibits Inflammation

MUC2 粘液凝胶作为抑制炎症的先天免疫机制

• 批准号: 9169944
• 负责人: Gunnar C. Hansson
• 金额: $ 30.56万
• 依托单位: GOTEBORG UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-22 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9169944
• 关键词: Address; Anabolism; Antigens; Area; Bacteria; Biochemical; Biological; Biology; Biopsy; Body Surface; Cell physiology; Cells; Colitis; Colon; Defect; Dendritic Cells; Development; Disease; Epithelial; Epithelial Cells; Exposure to; Gel; Genes; Germ-Free; Gluten; Goblet Cells; Health; Healthcare Systems; Homeostasis; Immune; Immune response; Immune system; Immunology; Inflammation; International; Intestines; Investments; Lamina Propria; Large Intestine; Life; Lysine; Mass Spectrum Analysis; Mediating; Meprin; Methods; Modeling; Molecular; Muc 2 protein; Mucin-2 Staining Method; Mucins; Mucous body substance; Pathway interactions; Patients; Peptide Hydrolases; Positioning Attribute; Process; Property; Proteins; Recombinants; Research; Role; Surface; System; Time; Transgenic Mice; Transglutaminases; Ulcerative Colitis; Western World; Work; adaptive immunity; cell type; cost; disulfide bond; glycosylation; improved; interest; knockout animal; microbial; mouse model; novel; transmission process; uptake

SUMMARY The mucus covering our mucosal surfaces is an intimate part of the innate immune system and the first line of defense against microbial challenges. This is especially prominent in the lower parts of the intestine where we have to protect ourselves at the same time as we live in a symbiotic relation without trigger an overt immune response. We have shown that colon has a double-layered mucus layer built around the MUC2 mucin. The inner of these act as a barrier and does not allow bacteria to penetrate. With an absence of MUC2 or defects in the mucus, bacteria reach the epithelial cells, penetrate into the crypts, and into the epithelial cells. In experimental colitis models this inner mucus layer is penetrable to bacteria and in patients with active colitis. This renewal is to continue studies on how the mucus layers are formed and built by the use of biochemical methods, especially mass spectrometry, and the use of various types of gene knock-out animals that are colonized with bacteria or germ-free. Patient studies on biopsies will follow changes in penetrability processes over the cyclic changes observed ulcerative colitis. The role of different mucus proteins on mucus properties will be studied and manipulated by recombinant mucus proteins and pharmacological agents. The three aims that will be studied are: Aim 1: To obtain a deeper functional and molecular understanding of the small intestinal mucus and its main component the MUC2 mucin in relation to mucus detachment, bacterial selection, and goblet cell uptake of antigens via transglutamination. Aim 2. To obtain a functional and cell biological understanding of the many different types of goblet cells in the intestine and their different secretory machinery. Aim 3. To obtain a functional understanding of how the mucus and its main components protect the mucosal surfaces of colon and inhibits ulcerative colitis. Expected results are novel ways to improve the protection of colon and by novel principles of the intestinal mucosal immunology that could have importance for understanding the disease ulcerative colitis.

总结 覆盖我们粘膜表面的粘液是先天免疫系统的一个重要组成部分， 系统和抵御微生物挑战的第一道防线。这是特别 在肠道的下部突出，我们必须保护自己， 与此同时，我们生活在一种共生关系中，而不会引发明显免疫 反应我们已经证明，结肠有一个双层粘液层， MUC2粘蛋白。这些内部充当屏障，不允许细菌 穿透。如果粘液中没有MUC2或有缺陷，细菌就会到达粘膜。 上皮细胞，渗透到隐窝，并进入上皮细胞。实验性 结肠炎模型这种内部粘液层是可穿透的细菌， 活动性结肠炎这次更新是为了继续研究粘液层是如何形成的 并通过使用生物化学方法，特别是质谱法， 使用各种类型的基因敲除动物，这些动物体内定植有细菌或 无菌的对活检的患者研究将遵循穿透性过程的变化 观察到溃疡性结肠炎的周期性变化。不同粘液的作用 将研究蛋白质对粘液性质的影响， 蛋白质和药理学试剂。将研究的三个目标是：目标1： 为了更深入地了解小肠的功能和分子 粘液及其主要成分MUC2粘蛋白与粘液脱离有关， 细菌选择和杯状细胞通过转谷氨酰胺摄取抗原。目标2. 为了获得许多不同类型的功能和细胞生物学的理解， 肠中的杯状细胞及其不同的分泌机制。目标3.为了获得 了解粘液及其主要成分如何保护 结肠粘膜表面和抑制溃疡性结肠炎。预期结果新颖 方法来改善结肠的保护和肠道的新原则， 粘膜免疫学可能对了解这种疾病有重要意义 溃疡性结肠炎