Regulation of cell fate by a novel p53-inducible ligand-independent TRAIL-R2 complex

皮肤、肠道(肠道)和其他器官(如肺)表面(上皮)屏障功能的维持对健康至关重要。在皮肤中，屏障功能对于强健、健康、保湿的皮肤是必不可少的，并保护活细胞免受环境化学物质、生物刺激物和感染剂的进入。在肠道中，上皮屏障调节营养吸收，并防止病原菌感染。当屏障功能受损时，可能会导致炎症、感染，最终导致器官功能丧失。因此，为了应对一系列因素造成的损害，如皮肤中的紫外线辐射和食物中的感染性物质和毒素，这些器官的上皮细胞必须以高度调控的方式对损害做出反应，而不损害屏障功能。我们发现了一种新的内部细胞机制，它是对细胞应激的早期反应，严格控制上皮细胞的死亡。我们假设，面对上皮表面每天遇到的各种环境破坏，这种机制对生物体的健康至关重要，它通过防止大量上皮细胞死亡，最终导致皮肤、肠道和其他组织中关键屏障功能的丧失。通过在基本分子水平上研究这一机制，我们旨在为维持皮肤和肠道健康提供见解，从而为保护这些重要屏障和抗击这些屏障受损的疾病提供新的方法；这些疾病包括皮肤的炎症性疾病(例如特应性皮炎和牛皮癣)和肠道(例如炎症性肠病，IBD)。这些研究还可能对其他重要的上皮屏障产生影响，比如肺部衬里的屏障，炎症可能会导致哮喘等危及生命的疾病。

The maintenance of the barrier functions of the surfaces (epithelia) of the skin, intestines (gut) and other organs (for example, lung) are critical for health. In the skin, the barrier function is essential for strong, healthy, hydrated skin and protects living cells against environmental chemicals, biological irritants and entry of infectious agents. In the gut, the epithelial barrier regulates nutrient absorption as well as preventing infection by pathogenic bacteria. When barrier functions are compromised, this can lead to inflammation, infection and ultimately loss of organ function. Therefore, in response to damage caused by a range of agents, for example ultraviolet (UV) radiation in the skin and infectious agents and toxins in food, the epithelial cells of these organs must respond in a highly regulated manner to the damage in a way that does not compromise barrier function.We have identified a novel internal cellular mechanism that is activated as an early response to cellular stress, which tightly controls the death of epithelial cells. We hypothesize that this mechanism is essential for organismal health in the face of the sorts of environmental damage that epithelial surfaces encounter on a daily basis, by preventing mass epithelial cell death, which would ultimately lead to loss of critical barrier functions in the skin, gut and other organs.By studying this mechanism at a fundamental molecular level, we aim to provide insights into the maintenance of skin and intestinal health that could inform new ways of protecting these vital barriers and combating diseases in which these barriers become compromised; these include inflammatory diseases of the skin (e.g. atopic dermatitis and psoriasis) and gut (e.g. inflammatory bowel disease, IBD). These studies could also have implications for other important epithelial barriers like those in the lining of the lungs, where inflammation can result in life-threatening conditions like asthma.