Intestinal epithelial cells (IECs) are continuously exposed to large numbers of commensal bacteria but relatively insensitive them, thereby averting an excessive inflammatory reaction. We have previously reported that the hyporesponsiveness a human IEC line LPS was primarily result down-regulation TLR4 gene transcription through epigenetic mechanisms. In present study we show DNA methylation in 5' region is significantly higher IECs than splenic vivo. The shown be dependent on...

It has been demonstrated that intestinal commensal bacteria induce immunoglobulin (Ig) A production by promoting the development of gut-associated lymphoid tissues in small intestine. However, precise mechanism whereby these modulate IgA large intestine, which harbors majority commensals, is poorly understood. In addition, it not known intestine and To address issues, we generated gnotobiotic mice mono-associated with different murine inoculating germ-free (GF) Lactobacillus johnsonii or...

The intestinal tract contains many commensal bacteria that modulate various physiological host functions. Dysbiosis of triggers dysfunction the epithelial barrier, leading to induction or aggravation inflammation. To elucidate whether microRNA plays a role in microbiome-dependent barrier regulation, we compared transcripts cells (IECs) from conventional and germ-free mice found induced expression miR-21-5p IECs. increased permeability up-regulated ADP ribosylation factor 4 (ARF4), small...

Foxp3 plays an important role in the development and function of regulatory T cells (Treg). Both induction maintenance gene expression are controlled by several regions including two enhancers conserved noncoding sequences (CNS). The functions Enhancer 1 CNS1 well established, whereas those 2 CNS2 remain unclear. Although contains enhancer activity, methylated CpG this region prevent Foxp3(-) cells. These are, however, demethylated Foxp3(+) Treg mechanisms as yet unknown. To investigate...

The gut mucosal immune system is crucial in host defense against infection by pathogenic microbacteria and viruses via the production of IgA. Previous studies have shown that intestinal commensal bacteria enhance IgA production. However, it poorly understood how these induce which genera effectively. In this study, we compared immunomodulatory effects Bacteroides Lactobacillus on Peyer's patches lymphocytes. lymphocytes co-cultured with was higher than Lactobacillus. addition, expression...

Fructo-oligosaccharides (FOS) are prebiotic agents with immunomodulatory effects involving improvement of the intestinal microbiota and metabolome. In this study, we investigated cellular mechanisms through which FOS modulate antigen-specific CD4+ T cell responses in food allergy, using OVA23-3 mice.OVA23-3 mice were fed an experimental diet containing either ovalbumin (OVA) or OVA for 1 week. Body weight mucosal mast protease serum measured as indicator inflammation. Single-cell suspensions...

SARS-CoV-2 causes a spectrum of clinical symptoms from respiratory damage to gastrointestinal disorders. Intestinal infection triggers immune response. However, the cellular mechanism that how initiates and induces intestinal immunity is not understood. Here, we exploited SARS-CoV-2-GFP/ΔN trVLP pseudo-virus system demonstrated RIG-I DHX15 are required for sensing inducing response through MAVS signaling in epithelial cells (IECs) upon infection. NLRP6 also engages regulation by producing...

Abstract TL1A contributes to the pathogenesis of several chronic inflammatory diseases, including those bowel by enhancing TH1, TH17, and TH2 responses. mediates a strong costimulation these TH subsets, particularly mucosal CCR9+ T cells. However, signaling pathways that induces in different subsets are incompletely understood. We investigated function on human TH17 TL1A, together with TGF-β, IL-6, IL-23, enhanced secretion IL-17 IFN-γ from CD4+ memory induced expression transcription...

Abstract α-Defensin 5 is important to both maintenance of a gut microbiota and host immunity. While previous reports have shown that bacteria are able upregulate α-defensin through Toll-like receptor signaling, we demonstrate here expression can also be regulated by microbial metabolites. Among these, lactate appeared significantly suppress gene transcription. Actually, fractions <3 kD compounds obtained from the ceca SPF mice were suppressed transcription at specific concentrations....

Abstract Glucocorticoid-induced TNFR (Gitr) and Ox40, two members of the superfamily, play important roles in regulating activities effector regulatory T cells (Treg). Their gene expression is induced by cell activation further upregulated Foxp3+ Treg. Although role Foxp3 as a transcriptional repressor Treg well established, mechanisms underlying Foxp3-mediated upregulation remain poorly understood. This transcription factor seems to upregulate not only Gitr but also other genes, including...

The intestine is inhabited by a large number of commensal bacteria that are immunologically non-self, potentially causing inflammation. However, in healthy intestine, inflammation strictly controlled at low levels to maintain homeostasis. We previously reported the gut microbiota induce DNA methylation gene encoding Toll-like receptor (TLR) 4, pattern recognition recognizes lipopolysaccharides gram-negative bacteria, colonic epithelial cells, suggesting its role controlling intestinal there...

Immune responses against gut microbiota should be minimized to avoid unnecessary inflammation at mucosal surface. In this study, we analyzed the expression patterns of Toll-interacting protein (Tollip), an inhibitor TLRs and IL-1 family cytokine-related intracellular signaling, in intestinal epithelial cells (IECs). Comparable mRNA was observed murine small large IECs (S-IECs L-IECs). However, Tollip only detected L-IECs, but not S-IECs. Similar results were obtained germ-free mice,...

Introduction The maintenance of intestinal homeostasis depends on a complex interaction between the immune system, epithelial barrier, and microbiota. Alteration in one these components could lead to development inflammatory bowel diseases (IBD). Variants within autophagy gene ATG16L1 have been implicated susceptibility severity Crohn’s disease (CD). Individuals carrying risk T300A variant higher caspase 3-dependent degradation resulting impaired increased cellular stress. ATG16L1-deficiency...

A huge number of commensal bacteria inhabit the intestine, which is equipped with largest immune system in body. Recently, regulation various physiological functions host by these has attracted attention. In this study, effects on gene expression colonic epithelial cells (CoECs) were investigated focus DNA methylation. RNA sequencing analyses CoECs from conventional, germ-free, and MyD88-/- mice indicated that, out genes affected bacteria, those downregulated a MyD88-independent manner most...

The oxytocin receptor (OXTR) knockout mouse is a model of autism spectrum disorder, characterized by abnormalities in social and olfactory behaviors learning. Previously, we demonstrated that OXTR plays crucial role regulating aversive behavior to butyric acid odor. In this study, attempted determine whether coffee aroma affects the abnormal OXTR-Venus knock-in heterozygous mice [heterozygous (±) mice] using set behavioral molecular experiments. Four-week repeated exposures odor, containing...

Summary Granulocytes from human peripheral blood were co-cultured with conventional dendritic cells (cDC) or plasmacytoid DCs (pDC) to examine the effects of on activation function granulocytes. After co-culture granulocytes DCs, expression markers (CD63 and CD64) was up-regulated, increased CD50, marker ligand for CD209 (DC-SIGN) also observed. The interaction visualized as cluster where especially cDCs, surrounded by form a ‘rosette’. secretion elastase enhanced significantly when examined...

The transcription factor FOXP3 plays key roles in the development and function of regulatory T cells (Treg) capable preventing correcting immunopathology. There has been much interest exploiting Treg as adoptive cell therapy man, but issues lack nominal antigen-specificity stability FoxP3 expression. In order to enable fundamental studies human (hFOXP3) gene regulation, provide preclinical tools guide selection drugs that might modulate hFOXP3 expression for therapeutic purposes, we...

Resistant maltodextrin (RMD) is a soluble dietary fibre that exerts several physiological functions as result of its microbial degradation and changes in the intestinal environment. It has been reported RMD enhanced immunoglobulin A (IgA) secretion, which protects mucosa from foreign substances. However, effect on excessive immunity yet to be investigated. In this study, we aimed investigate immune responses such food allergy. OVA23-3 mice were fed an AIN-76-based diet containing 20%...

Gut-associated lymphoid tissue (GALT), such as Peyer’s patches (PPs), are key inductive sites that generate IgA+ B cells, mainly through germinal center (GC) responses. The generation of cells is promoted by the presence gut microbiota and dietary antigens. However, function GALT in large intestine, cecal (CePs) colonic (CoPs), their regulatory mechanisms remain largely unknown. In this study, we demonstrate CePs possess more IgG2b+ have fewer than those PPs from BALB/c mice with normal...

Immunoglobulin (Ig) G isotypes in the sera of healthy mice and humans react to commensal bacteria. We previously reported that BALB/c with normal gut microbiota possessed abundant B cells produced IgG2b reactive bacteria cecal patches (CePs), indicating a potential source systemic pool bacteria-reactive IgG2b. Mice housed under germ-free conditions demonstrate importance driving responses. However, it is unclear whether constitutive presence specific bacterial taxa are important for...