Aryl hydrocarbon receptor (AhR) regulates both innate and adaptive immune responses by sensing a variety of small synthetic and natural chemicals, which act as its ligands. AhR, which is expressed in dendritic cells (DCs), regulates the differentiation of DCs. However, effects of AhR on the differentiation of DCs are variable due to the heterogeneity of DCs in cell surface marker expression, anatomical location, and functional responses. The plasmacytoid DCs (pDCs), one of DC subsets, not only induce innate as well as adaptive immune responses by secreting type I interferons and pro-inflammatory cytokines, but also induce IL-10 producing regulatory T cell or anergy or deletion of antigen-specific T cells. We showed here that AhR ligands indoxyl 3-sulfate (I3S) and indole-3-carbinol (I3C) inhibited the development of pDCs derived from bone marrow (BM) precursors induced by FMS-like tyrosine kinase 3 ligand (Flt3L). I3S and I3C downregulated the expression of signal transducer and activator of transcription 3 (STAT3) and E2-2 (Tcf4). In mice orally treated with I3S and I3C, oral tolerance to dinitrofluorobenzene was impaired and the proportion of CD11c⁺B220⁺ cells in mesenteric lymph nodes was reduced. These data demonstrate that AhR negatively regulates the development of pDCs from BM precursors induced by Flt3L, probably via repressing the expression of STAT3.
Animals ; Bone Marrow ; Cell Differentiation ; Cytokines ; Dendritic Cells* ; Dinitrofluorobenzene ; fms-Like Tyrosine Kinase 3* ; Immune Tolerance ; Interferon Type I ; Interleukin-10 ; Ligands* ; Lymph Nodes ; Mice ; Population Characteristics ; Receptors, Aryl Hydrocarbon* ; STAT3 Transcription Factor ; T-Lymphocytes ; Vascular Endothelial Growth Factor Receptor-1*

Th17 cells promote inflammatory reactions, whereas regulatory T (Treg) cells inhibit them. Thus, the Th17/Treg cell balance is critically important in inflammatory diseases. However, the molecular mechanisms underlying this balance are unclear. Here, we demonstrate that casein kinase 2 (CK2) is a critical determinant of the Th17/Treg cell balance. Both the inhibition of CK2 with a specific pharmacological inhibitor, CX-4945, and its small hairpin RNA (shRNA)-mediated knockdown suppressed Th17 cell differentiation but reciprocally induced Treg cell differentiation in vitro. Moreover, CX-4945 ameliorated the symptoms of experimental autoimmune encephalomyelitis and reduced Th17 cell infiltration into the central nervous system. Mechanistically, CX-4945 inhibited the IL-6/STAT3 and Akt/mTOR signaling pathways. Thus, CK2 has a crucial role in regulating the Th17/Treg balance.
Casein Kinase II* ; Casein Kinases* ; Caseins* ; Central Nervous System ; Encephalomyelitis, Autoimmune, Experimental ; In Vitro Techniques ; RNA, Small Interfering ; T-Lymphocytes, Regulatory* ; Th17 Cells

Naive CD4 T cells activated by antigen-presenting cells (APCs) undergo terminal differentiation in the periphery. Multiple mechanisms determine their fates, that is, whether they differentiate into conventional T (Tconv) cells or regulatory T (Treg) cells. The key event during Treg generation is expression of the transcription factor Foxp3, which is the lineage-determining regulator for Treg differentiation and function. Here we show that the transcription factor Batf3 acts as a fate-decision factor with respect to Tconv versus Tregs by restraining Treg differentiation. Batf3 was preferentially expressed in effector CD4 T cells but not in Treg cells, and ectopic expression of Batf3 inhibited Foxp3 induction. Batf3-deficient CD4 T cells favorably differentiated into Treg cells in vitro and in colonic lamina propria. Batf3 KO mice also showed enhanced Treg function in gut-associated immune disease models (for example, ovalbumin tolerance and inflammatory bowel disease models). Batf3 bound to the CNS1 region of the Foxp3 locus and reduced expression of the gene. Thus, Batf3 is a transcriptional suppressor of Treg differentiation.
Animals ; Antigen-Presenting Cells ; Colon ; Ectopic Gene Expression ; Immune System Diseases ; In Vitro Techniques ; Inflammatory Bowel Diseases ; Mice ; Mucous Membrane ; Ovalbumin ; T-Lymphocytes ; T-Lymphocytes, Regulatory* ; Transcription Factors*

BACKGROUND: The bacterium Chlamydia trachomatis is one of the leading causes of sexually transmitted diseases worldwide. Since no simple and effective tool exists to diagnose C. trachomatis infections, we evaluated a novel point-of-care (POC) test, aQcare Chlamydia TRF kit, which uses europium-chelated nanoparticles and a time-resolved fluorescence reader. METHODS: The test performance was evaluated by comparing the results obtained using the novel POC testing kit with those obtained using a nucleic acid amplification test (NAAT), using 114 NAAT-positive and 327 NAAT-negative samples. RESULTS: The cut-off value of the novel test was 20.8 with a detection limit of 0.27 ng/mL. No interference or cross-reactivity was observed. Diagnostic accuracy showed an overall sensitivity of 93.0% (106/114), specificity of 96.3% (315/327), positive predictive value (PPV) of 89.8% (106/118), and negative predictive value (NPV) of 97.5% (315/323). The sensitivity of the novel test was much higher than that of currently available POC tests. Furthermore, the relative ease and short turnaround time (30 min) of this assay enables C. trachomatis-infected individuals to be treated without a diagnostic delay. CONCLUSIONS: This simple and novel test is a potential tool to screen a larger population, especially those in areas with limited resources.
Adult ; Aged ; Aged, 80 and over ; Chlamydia Infections/*diagnosis ; Chlamydia trachomatis/*genetics/isolation & purification ; DNA, Bacterial/chemistry/metabolism ; Europium/*chemistry ; Female ; Humans ; Male ; Metal Nanoparticles/*chemistry ; Middle Aged ; Point-of-Care Systems ; Reagent Kits, Diagnostic ; Real-Time Polymerase Chain Reaction ; Sensitivity and Specificity ; Young Adult

An educational application (App) called 'Children's Food Avatar' was developed in this study by using a food DB of nutrition and functionality from Rural Development Administration (RDA) as a smart-learning mobile device for elementary school students. This App was designed for the development of children's desirable dietary habits through an on-line activity of food choices for a meal from food DB of RDA provided as Green Water Mill guide. A customized avatar system was introduced as an element of fun and interactive animation for children which provides nutritional evaluation of selected foods by changing its appearance, facial look, and speech balloon, and consequently providing chances of correcting their food choices for balanced diet. In addition, nutrition information menu was included in the App to help children understand various nutrients, their function and healthy dietary life. When the App was applied to 54 elementary school students for a week in November, 2012, significant increases in the levels of knowledge, attitude and behavior in their diet were observed compared with those of the control group (p < 0.05, 0.01). Both elementary students and teachers showed high levels of satisfaction ranging from 4.30 to 4.89 for the App, therefore, it could be widely used for the dietary education for elementary school students as a smart-learning device.
Child ; Diet ; Food Habits ; Humans ; Meals ; Nutrition Policy ; Social Planning

Patients' insight has a critical role in the recovery from problematic behavior. The aim of this study was to evaluate the effects of a brief intervention to promote insight among alcohol-dependent patients. A total of 41 alcohol-dependent patients (30 males, 11 females) in an insight-deficient state who had been admitted to a community-based alcohol treatment center, were randomized into two groups based on their admission order: an intervention group (IG) (n = 20) and a control group (CG) (n = 21). Patients in both the IG and CG participated in an identical treatment program with one exception: patients in the IG were required to undergo five sessions of brief individual intervention focusing on insight enhancement. Changes in insight state were assessed after the intervention. The IG exhibited significant (P < 0.05) changes in the distribution of insight level, while the CG did not exhibit any significant changes in the distribution of insight level. The insight score after intervention was significantly (P < 0.05) greater for the IG than the CG with adjustment for the baseline characteristics. The results suggest that a brief individual intervention focused on insight enhancement may be an effective tool to improve insight among alcohol-dependent patients.
Adult ; Alcohol-Related Disorders/*therapy ; Female ; Humans ; Interviews as Topic ; Male ; Middle Aged ; Patient Education as Topic

Patients' insight has a critical role in the recovery from problematic behavior. The aim of this study was to evaluate the effects of a brief intervention to promote insight among alcohol-dependent patients. A total of 41 alcohol-dependent patients (30 males, 11 females) in an insight-deficient state who had been admitted to a community-based alcohol treatment center, were randomized into two groups based on their admission order: an intervention group (IG) (n = 20) and a control group (CG) (n = 21). Patients in both the IG and CG participated in an identical treatment program with one exception: patients in the IG were required to undergo five sessions of brief individual intervention focusing on insight enhancement. Changes in insight state were assessed after the intervention. The IG exhibited significant (P < 0.05) changes in the distribution of insight level, while the CG did not exhibit any significant changes in the distribution of insight level. The insight score after intervention was significantly (P < 0.05) greater for the IG than the CG with adjustment for the baseline characteristics. The results suggest that a brief individual intervention focused on insight enhancement may be an effective tool to improve insight among alcohol-dependent patients.
Adult ; Alcohol-Related Disorders/*therapy ; Female ; Humans ; Interviews as Topic ; Male ; Middle Aged ; Patient Education as Topic

Biliary strictures can be caused by various diseases. Intrahepatic duct (IHD) strictures are usually related to IHD stones and cholangitis. However, focal IHD strictures without IHD stones often create diagnostic problems. Parasitic diseases such as clonorchiasis can be a rare cause of an IHD stricture. Human clonorchiasis (Clonorchis sinensis infection) is an endemic parasitic disease in Eastern Asia, including Korea, and patients acquire the infestation by eating raw fish. On radiological examinations, clonorchiasis shows typically diffuse, minimal, or mild dilatation of the small IHD, particularly in the periphery, without dilatation of the extrahepatic duct. However, diagnosis of clonorchiasis can sometimes be difficult when radiological changes are atypical. We report a case of focal left IHD dilatation caused by clonorchiasis that was confused with a malignancy.
Bile Ducts, Intrahepatic ; Cholangiocarcinoma ; Cholangitis ; Clonorchiasis ; Constriction, Pathologic ; Dilatation ; Eating ; Far East ; Humans ; Korea ; Liver Neoplasms ; Parasitic Diseases ; Cholangiocarcinoma

Biliary strictures can be caused by various diseases. Intrahepatic duct (IHD) strictures are usually related to IHD stones and cholangitis. However, focal IHD strictures without IHD stones often create diagnostic problems. Parasitic diseases such as clonorchiasis can be a rare cause of an IHD stricture. Human clonorchiasis (Clonorchis sinensis infection) is an endemic parasitic disease in Eastern Asia, including Korea, and patients acquire the infestation by eating raw fish. On radiological examinations, clonorchiasis shows typically diffuse, minimal, or mild dilatation of the small IHD, particularly in the periphery, without dilatation of the extrahepatic duct. However, diagnosis of clonorchiasis can sometimes be difficult when radiological changes are atypical. We report a case of focal left IHD dilatation caused by clonorchiasis that was confused with a malignancy.
Bile Ducts, Intrahepatic ; Cholangiocarcinoma ; Cholangitis ; Clonorchiasis ; Constriction, Pathologic ; Dilatation ; Eating ; Far East ; Humans ; Korea ; Liver Neoplasms ; Parasitic Diseases ; Cholangiocarcinoma

TGF-beta-induced tolerogenic-antigen presenting cells (Tol-APCs) could induce suppression of autoimmune diseases such as collagen-induced arthritis (CIA) and allergic asthma. In contrast, many studies have shown that NKT cells are involved in the pathogenesis of Th1-mediated autoimmune joint inflammation and Th2-mediated allergic pulmonary inflammation. In this study, we investigated the effect of CD1d-restricted NKT cells in the Tol-APCs-mediated suppression of autoimmune disease using a murine CIA model. When CIA-induced mice were treated with Tol-APCs obtained from CD1d+/- or CD1d-/- mice, unlike CD1d+/- APCs, CD1d-/- Tol-APCs failed to suppress CIA. More specifically, CD1d-/- Tol-APCs failed to suppress the production of inflammatory cytokines and the induction of Th2 responses by antigen-specific CD4 T cells both in vitro and in vivo. Our results demonstrate that the presence of CD1d-restricted NKT cells is critical for the induction of Tol-APCs-mediated suppression of CIA.
Animals ; Antibodies/blood ; Antibody Formation/immunology ; Antibody Specificity/immunology ; Antigen-Presenting Cells/*immunology ; Antigens, CD1d/immunology ; Arthritis, Experimental/blood/*immunology/*prevention & control ; Collagen Type II/immunology ; Cytokines/blood ; Immune Tolerance/*immunology ; Inflammation Mediators/blood ; Mice ; Natural Killer T-Cells/*immunology ; Th1 Cells/immunology