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Biology subjects

Hughes, F. J.

Publications and source records attributed to Hughes, F. J..

2 recordsLinked to original sources

Identification of lactate as a potential inhibitory factor within epithelial cell supernatant and its effects on type 2 T cell populations

Abstract / Short SummaryEpithelial cells have been shown previously to inhibit release of type 2 cytokines from T cells and this process could be important in a type 2-mediated diseases such as asthma. Factors secreted by epithelial cells could regulate inflammatory responses and release an all is well signal such that the immune system is controlled. Here we show that lung epithelial cells are able to inhibit IL-2 driven type 2 cytokine release by PBMC cells across a transwell indicating the involvement of soluble mediators. We then fractionate the mediators within the conditioned media using methanol chloroform separation and size fractionation. Inhibitory activity was demonstrated within the polar fraction of supernatant separated by methanol chloroform extraction. We then found that lactate, a component within the polar fraction was able to mediate inhibition of the type 2 cytokines. The inhibitory activity of lactate deserves further study and could play a role in the inhibition of T cell derived cytokines in vivo.

immunology↗

Epigenetic findings in periodontitis in UK twins: a cross sectional study

BackgroundGenetic and environmental risk factors contribute to periodontal disease, but the underlying susceptibility pathways are not fully understood. Epigenetic mechanisms are malleable regulators of gene function that can change in response to genetic and environmental stimuli, thereby providing a potential mechanism for mediating risk effects in periodontitis. The aim of this study is to identify epigenetic changes across tissues that are associated with periodontal disease.\n\nMethodsSelf-reported gingival bleeding and history of gum disease, or tooth mobility, were used as indicators of periodontal disease. DNA methylation profiles were generated using the Infinium HumanMethylation450 BeadChip in whole blood, buccal, and adipose tissue samples from predominantly older female twins (mean age 58) from the TwinsUK cohort. Epigenome-wide association scans (EWAS) of gingival bleeding and tooth mobility were conducted in whole blood in 528 and 492 twins, respectively. Subsequently, targeted candidate gene analysis at 28 genomic regions was carried out testing for phenotype-methylation associations in 41 (tooth mobility) and 43 (gingival bleeding) buccal, and 501 (tooth mobility) and 556 (gingival bleeding) adipose DNA samples.\n\nResultsEpigenome-wide analyses in blood identified one CpG-site (cg21245277 in ZNF804A) associated with gingival bleeding (FDR=0.03, nominal p-value=7.17e-8), and 58 sites associated with tooth mobility (FDR<0.05) with the top signals in IQCE and XKR6. Epigenetic variation at 28 candidate regions (256 CpG-sites) for chronic periodontitis showed a strong enrichment for association with periodontal traits, and signals in eight genes (VDR, IL6ST, TMCO6, IL1RN, CD44, IL1B, WHAMM, and CXCL1) were significant in both traits. The methylation-phenotype association signals validated in buccal samples, and a subset (25%) also validated in adipose tissue.\n\nConclusionsEpigenome-wide analyses in adult female twins identified specific DNA methylation changes linked to self-reported periodontal disease. Future work will explore the environmental basis and functional impact of these results to infer potential for strategic personalized treatments and prevention of chronic periodontitis.

genomics↗