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

维持皮肤、肠和其他器官（例如肺）表面（上皮细胞）的屏障功能对健康至关重要。在皮肤中，屏障功能对于强壮、健康、水润的皮肤至关重要，并保护活细胞免受环境化学物质、生物刺激物和感染因子的进入。在肠道中，上皮屏障调节营养吸收以及防止病原菌感染。当屏障功能受损时，这可能导致炎症，感染和最终器官功能丧失。因此，为了应对一系列因素造成的损伤，例如皮肤中的紫外线（UV）辐射以及食物中的传染性物质和毒素，这些器官的上皮细胞必须以高度调节的方式对损伤做出反应，而不会损害屏障功能。我们已经确定了一种新型的内部细胞机制，它作为对细胞应激的早期反应而被激活，严格控制上皮细胞的死亡我们假设，这种机制是必不可少的有机体的健康，面对各种环境损害，上皮表面遇到的日常基础上，通过防止大规模上皮细胞死亡，这将最终导致损失的关键屏障功能，在皮肤，肠道和其他器官。通过研究这种机制在一个基本的分子水平，我们的目标是提供关于维护皮肤和肠道健康的见解，这些见解可以为保护这些重要屏障和对抗这些屏障受损的疾病提供新的方法;这些疾病包括皮肤炎性疾病（例如特应性皮炎和牛皮癣）和肠道炎性疾病（例如炎性肠病，IBD）。这些研究也可能对其他重要的上皮屏障产生影响，如肺内衬中的上皮屏障，炎症可能导致危及生命的疾病，如哮喘。

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.