Understanding contributions of T cell determining factors in the pathogenesis of IBD
Prof. Adrian Hayday
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King's College London
The human intestine is vital in maintaining a person’s nutritional status. In order to do this, the bowel is lined by a specialised layer of absorptive cells called the epithelium which forms a barrier a single cell thick between the gut contents and the body. A breakdown in the integrity of this layer is thought to be one of the primary insults which leads to the development of inflammatory bowel disease (IBD).
Sitting within the epithelium are a highly specialised group of T cells, a type of white blood cell. Professor Hayday’s group have recently identified a new family of genes, called butyrophilins, which the epithelial cells use to attract these T cells to sit within the surface of the intestine and help maintain the integrity of the barrier. Studies in animal models demonstrate that when butyrophilin family members are deleted from the epithelium in mice, specific members of the T cell compartment are missing. The regulation of specialised T cells by butyrophilin proteins is also seen in humans.
Studies of these T cell populations in humans with IBD has demonstrated that the composition of T cells in the epithelial layer is altered from that of people without disease. We hypothesise that this is due to genetic alterations in the butyrophilin family members. We have identified two candidate genetic variants which change the function of butyrophilin proteins. This study aims to examine how these specific genes might affect the development and course of IBD.