Lancet
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Memory T cells are known to reside in peripheral non-lymphoid tissue, but how their presence within solid organ allografts affects transplant outcomes is not known. We have previously described how graft-versus-host (GVH) allorecognition by passenger CD4 T cells within MHC class II-mismatched bm12 heart grafts provokes antinuclear humoral autoimmunity in C57BL/6 recipient mice. Here we aimed to examine how such GVH recognition affects the alloresponse to allografts with greater mismatching. ⋯ Wellcome Trust Clinical Research Training Fellowship.
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Non-typhoidal Salmonella (NTS) causes invasive and frequently fatal disease in African children. Existing strategies to prevent, diagnose, and treat NTS disease are inadequate. An improved understanding of the biology of invasive Salmonella infection will facilitate the development of novel NTS control measures. Despite evidence in mice and man showing a clear role for host genetics in NTS susceptibility, there are no published studies investigating host genetic susceptibility to NTS in African populations. ⋯ Wellcome Trust.
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Survival for squamous cell carcinoma of the head and neck (SCCHN) has not improved substantially in recent years. Since radiotherapy is a cornerstone of treatment, it is crucial to identify ways to augment its efficacy, for which tumour metabolism is an attractive target. p53 is a metabolic mediator, and TP53 mutations are common in this disorder. We sought to investigate metabolic changes in SCCHN, to elucidate any correlation with TP53 status, and to determine whether targeted metabolic therapy might be used to potentiate the effects of radiation. ⋯ Cancer Research UK, Royal College of Surgeons of England.
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Innate immune cells are major targets of glucocorticoids as anti-inflammatory therapies. Glucocorticoids are metabolic hormones that provide natural feedback regulation of immune function. They are widely prescribed, but use is restricted by side-effects. Much of our knowledge about how glucocorticoids work comes from studies in mice. However, since mice are imperfect models of human macrophage biology, for example in inflammation, whether this knowledge can be directly translated to man is uncertain. We aimed to address this uncertainty. ⋯ Wellcome Trust.
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Ulcerative colitis is an established risk factor for colorectal cancer, also known as colitis-associated cancer. Existing colonoscopic-based surveillance has many disadvantages, so a new accurate, efficient, cost-effective screening test is needed. MicroRNAs (miRNAs) regulate gene expression and are dysregulated in a range of diseases, including ulcerative colitis and colorectal cancer. This study aimed to establish the miRNAs associated with colitis-associated cancer. ⋯ Royal College of Surgeons of England.