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

摘要 覆盖在我们粘膜表面的粘液是天然免疫的亲密部分。 系统和应对微生物挑战的第一道防线。这是特别的 突出在肠道的下部，在那里我们必须保护自己 同时我们生活在一种共生关系中，而不会引发一种公开的免疫 回应。我们已经证明，结肠周围有一层双层粘液层 MUC2粘蛋白。它们的内部起到了屏障的作用，不允许细菌 穿透。如果没有MUC2或粘液有缺陷，细菌就会到达 上皮细胞，穿透到隐窝，并进入上皮细胞。处于实验阶段 结肠炎模型这种内粘液层可以穿透细菌，在患有结肠炎的患者中 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。 并通过使用生化方法，特别是质谱学方法和 使用各种类型的基因敲除动物，这些动物定居在细菌或 无菌的。患者对活检的研究将跟随穿透性过程的变化 观察到溃疡性结肠炎的周期性变化。不同粘液的作用 重组粘液对蛋白质特性的影响将被研究和操纵。 蛋白质和药理制剂。将研究的三个目标是：目标1： 对小肠的功能和分子方面有更深入的了解 粘液及其主要成分MUC2粘蛋白与粘液脱落的关系， 细菌选择和杯状细胞通过转谷氨酰胺作用摄取抗原。目标2. 为了获得对许多不同类型的 肠道中的杯状细胞及其不同的分泌机制。目标3.获得一个 对粘液及其主要成分如何保护 改善结肠粘膜表面，抑制溃疡性结肠炎。预期结果是新奇的 改善结肠保护的方法和肠道的新原理 粘膜免疫学对了解该病可能具有重要意义 溃疡性结肠炎。

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.