Lancet
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Natural killer cell maturation markers in the human liver and expansion of an NKG2C+KIR+ population.
Selected populations of murine natural killer (NK) cells possess memory features to haptens, cytokines, and viruses. Liver-specific adhesion molecules CXCR6 and CD49a have been identified as surface markers in mice. In people, expansion of long-lived terminally differentiated NKG2C+ populations occur in the blood after viral infection. We aimed to compare intrahepatic and blood NK cell receptor expression to determine the existence of CD49a+ and CXCR6+ NK cells in human liver and define the maturation status of NKG2C+ NK cells at this site. ⋯ MRC Clinical Research Fellowship.
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Worldwide, obesity has doubled since 1980. WHO declares obesity as preventable and attributes the increase in prevalence to high consumption of energy-rich foods and decreased physical activity. Epidemiological and experimental studies suggest that parents' and grandparents' diet could also have a role. We established a model of grandparents' high-fat diet (HFD) to explore potential mechanisms. ⋯ UK Medical Research Council.
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Age-related macular degeneration is a leading cause of irreversible blindness. Altered immune responses drive degeneration, in response to oxidative stress and hypoxia-induced regulation of metabolism. We tested the hypothesis that toll-like receptor activation of retinal pigment epithelium and cellular metabolic switch upregulate interleukin 33, which acts through its receptor ST2 to activate both choroidal stromal fibroblasts and mast cells. By such mechanisms, the fibrosis and insidious degeneration, which we observe clinically, is accentuated. ⋯ National Institute for Health Research, National Eye Research Centre.
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Retinitis pigmentosa, which affects one in 3000 people, causes blindness and has no treatment. Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene cause 20% of all cases. Recent work suggests that RPGR, localised to the photoreceptor connecting cilium, regulates rhodopsin transport to the outer segment through its effect on the turnover of actin. We set out to establish a novel model for RPGR disease to test the hypothesis that RPGR mutations lead to retinal degeneration due to a dysregulation of the actin cytoskeleton. ⋯ Wellcome Trust.
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A single risk haplotype across UBE2L3 is strongly associated with systemic lupus erythematosus (SLE) and many other autoimmune diseases. UBE2L3 is an E2 ubiquitin-conjugating enzyme with specificity for RING-in-between-RING E3 ligases, including HOIL-1 and HOIP, components of the linear ubiquitin chain assembly complex (LUBAC), which has a pivotal role in inflammation, through crucial regulation of NF-κB. We aimed to determine whether UBE2L3 regulates LUBAC-mediated activation of NF-κB, and determine the effect of UBE2L3 genotype on NF-κB activation and B-cell differentiation. ⋯ Arthritis Research UK, Wellcome Trust, George Koukis Foundation, European Community's Seventh Framework Programme.