Involvement of Dectin-2 in the Innate Inflammatory Response Triggered by Influenza Virus Hemagglutinin

C-type lectin receptors (CLRs) are representative pattern recognition receptors that recognize microbial polysaccharides expressed on antigen-presenting cells. In the present study, we carried out further detailed analysis on the involvement of Dectin-2, a CLR that senses high mannose polysaccharide, in innate immune responses induced by influenza virus hemagglutinin (HA). Treatment of HA with periodate or PNGase F induced lower interleukin (IL)-12p40 secretion by conventional dendritic cells (DCs) compared with the untreated group. In contrast, treatment with O-glycosidase did not affect cytokine production. Green fluorescent protein expression in canonical Dectin-2-transducing cells was approximately 3% - 12% following HA stimulation, except with the A/H1N1pdm09 subtype HA. This expression was markedly reduced in cells possessing mutated amino acids in the carbohydrate recognition domain of Dectin-2, especially following stimulation with HA derived from the A/H3N2 subtype. Interferon (IFN)-α production from CD11c+Siglec-H+PDCA-1+ plasmacytoid DCs was significantly increased in Dectin-2 knockout mice compared with wild-type mice upon stimulation with HA except for the B/Yamagata lineage HA. These results suggested that Dectin-2 is involved in initiating inflammatory responses via mannose polysaccharide on HA. However, other mechanisms may function in the antiviral response, including the type I IFN axis.

Protective effect of alcohol consumption for fatty liver but not metabolic syndrome

AIM:To investigate the effect of alcohol on the metabolic syndrome (MS) and fatty liver in Japanese men and women.METHODS:A cross-sectional study was conducted in a medical health checkup program at a general hospital.This study involved 18 571 Japanese men and women,18-88 years of age,with a mean body mass index of 22.6 kg/m 2.A standardized questionnaire was administered.The total amount of alcohol consumed per week was calculated,and categorized into four grades.Fatty liver was examined by ultrasound modified criteria of the revised National Cholesterol Educa-tion Program Adult Treatment Panel Ⅲ and the new International Diabetes Federation.RESULTS:The prevalence of fatty liver decreased in men and women with light to moderate alcohol consumption,whereas the prevalence of MS was not so changed.The prevalence of fatty liver of any grade in men was lower than that in those with no or minimal alcohol consumption.In women with light to moderate alcohol consumption,prevalence of fatty liver was lower than that in women with no or minimal alcohol consumption.By logistic regression analysis,the odds ratio (OR) for MS in women with light alcohol consumption was decreased to < 1.0,but this change was not clear in men.The OR for fatty liver was clearly < 1.0 in men with any level of alcohol consumption and in women with light to moderate consumption.CONCLUSION:Light to moderate alcohol consumption has a favorable effect for fatty liver,but not for MS in Japanese men and women.

Identification of individuals with non-alcoholic fatty liver disease by the diagnostic criteria for the metabolic syndrome

AIM:To clarify the efficiency of the criterion of metabolic syndrome to detecting non-alcoholic fatty liver disease(NAFLD).METHODS:Authors performed a cross-sectional study involving participants of a medical health checkup program including abdominal ultrasonography.This study involved 11 714 apparently healthy Japanese men and women,18 to 83 years of age.NAFLD was defined by abdominal ultrasonography without an alcohol intake of more than 20 g/d,known liver disease,or current use of medication.The revised criteria of the National Cholesterol Education Program Adult Treatment PanelⅢ were used to characterize the metabolic syndrome.RESULTS:NAFLD was detected in 32.2%(95%CI:31.0%-33.5%)of men(n=1874 of 5811)and in 8.7%(95%CI:8.0%-9.5%)of women(n=514 of 5903).Among obese people,the prevalence of NAFLD was as high as 67.3%(95%CI:64.8%-69.7%)in men and 45.8%(95%CI:41.7%-50.0%)in women.Although NAFLD was thought of as being the liver phenotype of metabolic syndrome,the prevalence of the metabolic syndrome among subjects with NAFLD was low both in men and women.66.8%of men and 70.4%of women with NAFLD were not diagnosed with the metabolic syndrome.48.2%of men with NAFLD and 49.8%of women with NAFLD weren't overweight[body mass index(BMI)≥25 kg/m2].In the same way,68.6%of men with NAFLD and 37.9%of women with NAFLD weren't satisfied with abdominal classification(≥90 cm for men and≥80 cm for women).Next,authors defined it as positive at screening for NAFLD when participants satisfied at least one criterion of metabolic syndrome.The sensitivity of the definition"at least 1 criterion"was as good as 84.8%in men and 86.6%in women.Separating subjects by BMI,the sensitivity was higher in obese men and women than in non-obese men and women(92.3%vs 76.8%in men,96.1%vs 77.0%in women,respectively).CONCLUSION:Authors could determine NAFLD effectively in epidemiological study by modifying the usage of the criteria for metabolic syndrome.

Inhibition of IRF3-dependent antiviral responses by cellular and viral proteins

The host evokes innate immune responses to eliminate viruses by detecting the presence of infection. Host cells respond to nucleic acids derived from infected viruses to produce cytokines known as type I interferons （IFNβ and multiple IFNα）, which are the most important cytokines for host defense against viral infection. Type I interferons induce the synthesis of hundreds of IFN-inducible genes （ISG） that influence protein synthesis, growth arrest and cell death to induce the antiviral state as well as enhance dendritic cell maturation, natural killer cell activation,

Detection of Adhesion Molecules on Inflamed Macrophages at Early-Stage Using SERS Probe Gold Nanorods

In recent years, it has been shown that inflammatory biomarkers can be used as an effective signal for disease diagnoses. The early detection of these signals provides useful information that could prevent the occurrence of severe diseases. Here, we employed surface-enhanced Raman scattering(SERS) probe gold nanorods(GNRs) as a tool for the early detection of inflammatory molecules in inflamed cells. A murine macrophage cell line(Raw264.7) stimulated with lipopolysaccharide(LPS) was used as a model in this study. The prepared SERS probe GNRs containing 4-mercaptobenzoic acid as a Raman reporter to generate SERS signals were used for detection of intracellular adhesion molecule-1(ICAM-1) in macrophages after treatment with LPS for varying lengths of time. Our results show that SERS probe GNRs could detect significant differences in the expression of ICAM-1 molecules in LPS-treated macrophages compared to those in untreated macrophages after only 1 h of LPS treatment. In contrast, when using fluorescent labeling or enzyme-linked immunosorbent assays(ELISA) to detect ICAM-1, significant differences between inflamed and un-inflamed macrophages were not seen until the cells had been treated with LPS for 5 h. These results indicate that our SERS probe GNRs provide a higher sensitivity for detecting biomarker molecules in inflamed macrophages than the conventional fluorescence and ELISA techniques, and could therefore be useful as a potential diagnostic tool for managing disease risk.

Ultrasonic Image Registration for Multi-Frequency Analysis

This paper describes ultrasonic image registration for multi-frequency analysis. The goal of our research is the portable and real time brain diagnosis under the thick-skull. The choice of ultrasonic frequency is a trade-off between spatial image resolution and imaging depth. This study shows the usability of data synthesis by employing two different frequency ultrasounds. In the first part of this study, using Fast Fourier Transform, we conclude that the synthesized image was produced from two ultrasonic images of individual objects. The purpose of the second approach of the data synthesis is to investigate three methods of ultrasonic imaging. This approach is particular interest for the design of further study intending to visualize any defects by ultrasonic methods. As the results, the synthesized image with Wavelet transform has higher efficiency than the other synthesized ones for the bone and the sulcus. In summary, this study indicates that the ultrasonic synthesized image is useful to visualize the imitated brain area. This observation is encouraging for further studies of evaluating brain for patients.

Favorable effect of modest alcohol consumption to fatty liver disease

We previously reported that modest alcohol consumption was significantly inversely associated with fatty liver disease.Feng et al pointed out a discrepancy of statistical significance between our current larger scale cohort and a previous cohort.However,the prevalence of non-alcoholic fatty liver disease was higher in non or minimal drinkers than those in light drinkers in both cohorts.They also argue that some potential co-factors such as soft drink consumption and genetic variations should be discussed.

Metal Ion Release of Manufactured Metal Oxide Nanoparticles Is Involved in the Allergic Response to Inhaled Ovalbumin in Mice

The aim of the present study was to establish the mechanism of the allergy aggravation effect. Our previous study showed that soluble ZnO nanoparticles caused allergy aggravation, but insoluble TiO2 and SiO2 nanoparticles did not induce an allergic response. Metal ion release is associated with the cytotoxicity of manufactured nanoparticles;however, the role of metal ion release in allergy aggravation remains to be elucidated. Therefore, we examined the allergy aggravation potential of several soluble manufactured nanoparticles (ZnO, CuO, NiO, MgO, and CaCO3). These nanoparticles were administered to mouse lungs by pharyngeal aspiration and subsequently, the mice inhaled ovalbumin (OVA). We also compared the properties of soluble NiO nanoparticles with insoluble micro-scale NiO particles. NiO nanoparticles markedly increased the levels of OVAspecific immunoglobulin (Ig) E but micro-scale NiO particles did not. Among the nanoparticles (ZnO, CuO, MgO, and CaCO3), ZnO induced increase of OVA-specific IgE level. CuO showed tendency to increase OVA-specific IgE;however, no significant difference was observed. Additionally, ZnO and NiO nanoparticles enhanced expression of a gene related to inflammation (Cxcl2), heavy metal detox (metallothionein 2), and oxidative stress (heme oxygenase-1). Gene expression of arginase1, which is enhanced by T helper 2 cytokine, was remarkably enhanced in mice administered ZnO and NiO particles. These effects were not observed in mice administered MgO and CaCO3 nanoparticles. In conclusion, the solubility and type of metal ion released from the nanoparticles influence the allergy aggravation effect. The results showed that the release of Zn2+ and Ni2+ aggravated the allergic reaction.

The emerging role of Arid5a in cancer: A new target for tumors

AT-rich interactive domain 5a (Arid5a) is a member of the arid family of proteins, which contain a helix-turn-helix domain and an ability to bind to nucleic acids. Current evidence suggests that Arid5a performs dual functions as a transcription factor and an RNA-binding protein in immune, nonimmune, and/ or tumor cells depending on its cellular localization. The contribution of Arid5a to the development of inflammation, autoimmunity, and obesity through its transcriptional and posttranscriptional regulatory functions has broadly been reviewed. Recent studies have indeed revealed an association of Arid5a with cancers, including breast, pancreatic, colorectal, and lung cancers and glioma. Notably, Arid5a affects various aspects of cellular homeostasis, including invasion, metastasis, epithelial-to-mesenchymal transition, immune evasion, adipogenesis and M1-like tumor-associated macrophage (TAM)-to-M2-like TAM transition. This review aims to summarize current knowledge of Arid5a from a cancer perspective and highlights recent advances in Arid5a-related cancer research. This review may improve the understanding of Arid5a-mediated molecular mechanisms and their relevance to cancers.

Single-cell analysis for identification of T-cell clonotypes associated with IgG4 production of autoimmune pancreatitis

Introduction Autoimmune pancreatitis(AIP)is one of the recently established immunoglobulin G4-related diseases(IgG4-RD)[1].The detailed pathogenic mechanisms have been an intensive research area for prophylactic and therapeutic purposes because aberrant immune activation and tissue fibrosis in AIP are the major factors that worsen the disease outcomes in these patients.

Invariant natural killer T cells and iron metabolism orchestrate skin development and homeostasis

In recent years,innate-like T-cell populations,such as invariant natural killer T(iNKT)cells and mucosal-associated invariant T(MAIT)cells,have been identified[1].These cells are different from conventional T cells in that they reside in tissues such as the liver,lung,and skin,rather than the lymph node and spleen[2].Although iNKT and MAIT cells are abundant in the skin immediately after birth,the detailed functions or the mechanisms regulating their localization have not been clarified[3].In a study published in Nature Immunology,Wang et al.reported that the early homing of iNKT cells to the skin was dependent on CCR10 expression during the stage of thymic development and was critical for proper commensal bacterial colonization and skin development[4].

Nature:单核细胞SatM导致组织纤维化

在一项新的研究中，来自日本大阪大学免疫学前沿研究中心（IFReC）的研究人员报道了一类新的他们称之为SatM的单核细胞。针对小鼠的研究表明SatNI可能是导致组织纤维化的原因，而且成为一种治疗很少有有效疗法的疾病的新药物靶标。

Long noncoding RNA: TRIMming the viral load

Viruses are obligate intracellular entities that require a living host and its machinery for replication.During replication,viral components known as pathogen-associated molecular patterns(PAMPs)are sensed by a family of innate immune sensors or pattern recognition receptors(PRRs)and promote an antiviral state.Viral nucleic acids are one of the key PAMPs sensed by cytosolic RIG-I-like receptors(RLRs),Cyclic GMP-AMP Synthase(cGAS),Absent In Melanoma 2(AIM2),Interferon Gamma Inducible Protein 16(IFI16),and Z-DNA Binding Protein 1(ZBP1 or DAI)and endosome-localized Toll-like receptors(TLR3,7,8,and 9).1 Recognition of viral RNA by Retinoic acid-inducible gene I(RIG-I),Melanoma differentiation associated gene 5(MDA5),and TLR3,7,and 8 or viral DNA by TLR9,cGAS,AIM2,IFI16,and DAI triggers a cascade of signaling events to recruit transcription factors,interferon regulatory factors and NF-κB.Activated IRF3/7 and NF-κB translocate to the nucleus and induce expression of type I and III interferons and proinflammatory cytokines,respectively.1 The production of these interferons is further enhanced in an autocrine and paracrine manner through the JAK-STAT signaling pathway.Type I and III interferons further induce interferoninducible genes,and together with proinflammatory cytokines,they develop an antiviral state.The antiviral state is characterized by by apoptosis of virally infected cells and inhibition of the cellular protein synthesis machinery,making the uninfected cells resistant to viral infection and initiates virus-specific adaptive immune responses(Fig.1a).

Specific targeting of lung ILC2s via NRP1 in pulmonary fibrosis

Innate lymphoid cells are predominantly tissue-resident immune cells that have diverse functions similar to T-cell subsets and regulate tissue homeostasis and innate immunity without specific antigen recognition. Previous studies have reported the important roles of type 2 innate lymphoid cells (ILC2s) in allergic inflammation.