The carbohydrate response element binding protein (ChREBP), a basic helix-loop-helix/leucine zipper transcription factor, plays a critical role in the control of lipogenesis in the liver. To identify the direct targets of ChREBP on a genome-wide scale and provide more insight into the mechanism by which ChREBP regulates glucose-responsive gene expression, we performed chromatin immunoprecipitation-sequencing and gene expression analysis. We identified 1153 ChREBP binding sites and 783 target genes using the chromatin from HepG2, a human hepatocellular carcinoma cell line. A motif search revealed a refined consensus sequence (CABGTG-nnCnG-nGnSTG) to better represent critical elements of a functional ChREBP binding sequence. Gene ontology analysis shows that ChREBP target genes are particularly associated with lipid, fatty acid and steroid metabolism. In addition, other functional gene clusters related to transport, development and cell motility are significantly enriched. Gene set enrichment analysis reveals that ChREBP target genes are highly correlated with genes regulated by high glucose, providing a functional relevance to the genome-wide binding study. Furthermore, we have demonstrated that ChREBP may function as a transcriptional repressor as well as an activator.

PurposeProbiotic bacteria can induce immune regulation or immune tolerance in allergic diseases. The underlying mechanisms have been recently investigated, but are still unclear. The aim of this study was to evaluate the protective effects of the probiotic Lactobacillus rhamnosus (Lcr35) in a mouse model of asthma and to identify its mechanism of action.MethodsLcr35 was administered daily by the oral route at a dosage of 1×109 CFU/mouse in BALB/c mice for 7 days before the first sensitization. Clinical parameters and regulatory T (Treg) cells were examined. The role of CD4+CD25+Foxp3+ Treg cells was analyzed using a Treg cell-depleting anti-CD25 monoclonal antibody (mAb).ResultsAirway hyperresponsiveness, total IgE production, pulmonary eosinophilic inflammation, and splenic lymphocyte proliferation were suppressed after Lcr35 treatment. Th1 (IFN-γ) and Th2 (IL-4, IL-5, and IL-13) cytokines in the serum were suppressed, and the percentage of CD4+CD25+Foxp3+ Treg cells in the spleen was significantly increased in the Lcr35 treatment group. Anti-CD25 mAb administration abolished the protective effects of Lcr35, indicating that CD4+ CD25+Foxp3+ Treg cells are essential in mediating the activity of Lcr35.ConclusionsOral administration of Lcr35 attenuated the features of allergic asthma in a mouse model and induced immune regulation by a CD4+CD25+Foxp3+ Treg cell-mediated mechanism.

PurposeAlterations in the intestinal microbiota in early life affects the development of atopic dermatitis (AD) in humans. This study aimed to further investigate the effects of gut dysbiosis in early life in an ovalbumin (OVA)-induced mouse model of AD.MethodsThe AD mouse model was developed by serial OVA sensitization and mice were treated with an antibiotic cocktail in their drinking water for 2 weeks before primary sensitization. Probiotics (Lactobacillus rhamnosus, 1 × 109 CFU) or 100 µL of fresh fecal supernatant were orally administered daily from 1 week before the first sensitization until the end of the study.ResultsThe AD mice which received antibiotics had significantly aggravated phenotypes, including clinical score, transepidermal water loss, and histopathology, compared to those treated with healthy feces or probiotics. Total systemic immunoglobulin E production and skin interleukin (IL) 4 levels were significantly increased in the antibiotic-treated mice compared to the other groups. Antibiotic treatment also increased the levels of IL17 and group 3 innate lymphoid cells (ILC3) in the gut and significantly suppressed the production of short-chain fatty acids (SCFAs) and decreased the number FOXP3+ cells.ConclusionsOur results suggest that the status of the gut microbiota in early life in the mouse may play a crucial role in AD development through intestinal SCFA production through regulate the numbers of CD4+IL17+/CD4+FOXP3+ regulatory T cells and ILC3s.

PurposeThe aim of the present study was to investigate the relationship between three major allergic diseases, asthma, allergic rhinitis (AR), and atopic dermatitis (AD), and psychological and behavioural problems in preschoolers based on a community survey.MethodsA cross-sectional survey was conducted using a modified International Study of Asthma and Allergies in Childhood questionnaire to determine the prevalence of symptoms and diagnosed allergic diseases, and a Korean version of the Child Behaviour Checklist to assess internalizing, externalizing, and sleep problems among 780 preschoolers. Five-hundred and seventy-five preschoolers with valid data were included in this study.ResultsThe prevalence of lifetime diagnosis and treatment in the past 12 months was 8.7% and 4.4% for asthma, 24.4% and 19.2% for AR, and 35.1% and 16.6% for AD, respectively. Scores for internalizing and sleep problems were significantly higher in those diagnosed with AR. Preschoolers who had been treated for AD in the past 12 months had higher attention problem and attention-deficit/hyperactivity disorder scores. Sleep problems were more severe in moderate to severe AD compared to control and mild AD groups, categorised according to SCOring index of AD. The severity of sleep problems correlated positively with the percentage of eosinophils in peripheral blood.ConclusionsPsychological and behavioural problems differed among the three major allergic diseases, weaker association for asthma and stronger association for AR and AD. The results of this study may lead to the identification of potential underlying shared mechanisms common to allergic diseases and psychological and behavioural problems.