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

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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.