Like asthma and atopic dermatitis, allergic rhinitis is an allergic disease, but of the three, it is the only type I allergic disease. Allergic rhinitis includes pollinosis, which is intractable and reduces quality of life (QOL) when it becomes severe. A guideline is needed to understand allergic rhinitis and to use this knowledge to develop a treatment plan. In Japan, the first guideline was prepared after a symposium held by the Japanese Society of Allergology in 1993. The current 8th edition was published in 2016, and is widely used today. To incorporate evidence based medicine (EBM) introduced from abroad, the most recent collection of evidence/literature was supplemented to the Practical Guideline for the Management of Allergic Rhinitis in Japan 2016. The revised guideline includes assessment of diagnosis/treatment and prescriptions for children and pregnant women, for broad clinical applications. An evidence-based step-by-step strategy for treatment is also described. In addition, the QOL concept and cost benefit analyses are also addressed. Along with Allergic Rhinitis and its Impact of Asthma (ARIA), this guideline is widely used for various clinical purposes, such as measures for patients with sinusitis, childhood allergic rhinitis, oral allergy syndrome, and anaphylaxis and for pregnant women. A Q&A section regarding allergic rhinitis in Japan was added to the end of this guideline.

No abstract

No abstract

Background:The roles of ESRP1 and ESRP2 during carcinogenesis remain unknown. Results: ESRPs are up-regulated during carcinogenesis but down-regulated in invasive fronts. ESRP1 suppresses expression of the Rac1b isoform, whereas ESRP2 represses epithelial-mesenchymal transition-inducing transcription factors. Conclusion: ESRP1 and ESRP2 suppress cell motility through distinct transcriptional and/or post-transcriptional mechanisms. Significance: Our findings reveal a novel molecular network that regulates cancer cell motility.

We have studied the expression of the gene encoding the epsilon heavy chain of IgE in nasal B cells of hayfever patients. We developed probes to detect transcripts of the epsilon germ-line gene and the rearranged gene by in situ hybridization of biopsy sections from the nasal mucosa. We compared tissue from hayfever patients out of season with that of normal controls, and also of hayfever patients treated with topical corticosteroid (fluticasone propionate) or placebo for 6 weeks and then challenged with antigen. epsilon chain mRNA was expressed in an unexpectedly high proportion of nasal B cells of both hayfever patients and normal subjects. However, although similar numbers of B cells were found in both groups, the proportion of cells that express epsilon chain mRNA was several times higher in the hayfever patients. No transcripts of the epsilon germ-line gene were detected in either group before allergen challenge. When hayfever patients were administered antigen locally, early (10-30 min) and late (1-24 h) symptoms ensued. After 24 h, coincident with an increase in the number of cells expressing mRNA for IL-4 in the tissue, epsilon germ-line gene transcripts appeared in the nasal B cells. The induction by allergen of IL-4 mRNA and epsilon germ-line gene transcripts was suppressed by fluticasone propionate treatment. Our results suggest that local IgE synthesis and cytokine regulation of heavy chain switching to IgE occur in the nasal mucosa.

Myeloid‐derived suppressor cells (MDSC) represent a heterogeneous population and have the potential to suppress immune responses via diverse mechanisms. In recent studies, a new subset of MDSC was identified by the markers CD14+ and HLA‐DR− in the peripheral blood from cancer patients. In this study, we investigated the proportions and characteristics of CD14+ HLA‐DR− cells in patients with squamous cell carcinoma of the head and neck (SCCHN). As expected, the percentage of CD14+ HLA‐DR− cells was significantly elevated in patients relative to healthy donors and the sorted CD14+ HLA‐DR− cells were able to suppress effectively both the proliferation and IFN‐γ production of anti‐CD3/anti‐CD28 stimulated T cells, suggesting that CD14+ HLA‐DR− cells in patients with SCCHN contribute to the immune suppressive status. Furthermore, CD14+ HLA‐DR− cells revealed a higher level of CD86 and PD‐L1 expression and transforming growth factor (TGF)‐β production than CD14+ HLA‐DR+ cells. Addition of anti‐CD86 mAb, anti‐PD‐L1 mAb and anti‐TGF‐β mAb partially restored T‐cell proliferation and IFN‐γ production, respectively, indicating that the suppressive effects of CD14+ HLA‐DR− cells appear to be mediated by various molecules, including coinhibitory molecules and cytokines. Our data suggest that CD14+ HLA‐DR− cells act as potent immunosuppressive cells and particularly contribute to tumor escape from the host immune system in patients with SCCHN. (Cancer Sci 2012; 103: 976–983)

Epithelial cell-derived thymic stromal lymphopoietin (TSLP) is a master switch for asthma or atopic dermatitis by inducing a dendritic cell-mediated Th2-type allergic inflammation. Allergic rhinitis is also pathologically characterized by Th2-type allergic inflammation. This study demonstrates that mast cells regulate the epithelial TSLP expression in allergic rhinitis. TSLP expression was found to be up-regulated predominantly in the nasal epithelium in the ovalbumin (OVA)-sensitized and -nasally challenged mouse model of allergic rhinitis, which was abolished in mast cell-deficient WBB6F1-W/W v in comparison with control WBB6F1-+/+ mice. Similarly, the epithelial TSLP expression was reduced in Fc receptor c chain (FccR)-deficient mice, where the high-affinity IgE receptor (FceRI) is not expressed on mast cells, in comparison with control C57BL/6 mice. Furthermore, the administration of neutralizing TSLP antibody during the challenge phase of OVA inhibited the development of allergic rhinitis. These results suggest that the direct stimulation of epithelial cells by antigens alone may not be sufficient to induce TSLP expression in the nasal epithelium, and that mast cell regulation of epithelial TSLP expression, possibly via FceRI, plays an important role in the development of allergic rhinitis. Key words: Allergic rhinitis Á Epithelial cells Á Mast cells Á TSLP IntroductionThymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine, which binds to a TSLP receptor (TSLPR) consisting of the IL-7 receptor a-chain (IL-7Ra) and a common c receptor-like chain (TSLPR-c) [1,2]. TSLP was originally identified as a factor derived from a thymic stromal cell line that could support the growth of a mouse B cell line [3]. However, recently, TSLP, derived from epithelial cells, has been shown to be capable of activating CD11c + myeloid DC to up-regulate costimulatory molecules, leading to the differentiation of CD4 + T cells into Th2 cells. Therefore, it plays a key role in the development of allergic diseases such as asthma or atopic dermatitis [1,2,4]. For instance, transgenic mice expressing TSLP in keratinocytes or in lung epithelial cells have been shown to develop atopic dermatitis-or asthma-like inflammation in the skin or the lung, respectively, while TSLPR null mice failed to develop an inflammatory lung response to inhaled antigen [5][6][7]. In humans, TSLP has been shown to be expressed by keratinocytes in atopic dermatitis and by bronchial epithelial cells in asthmatic airways [8,9].In contrast to the pro-allergic action of TSLP, regulation of TSLP expression in epithelial cells has not been fully elucidated. Previous studies suggest that TSLP expression in mouse keratinocytes is regulated by vitamin D and retinoic acid signaling [10] [17]. In addition, mast cells up-regulate the production of a variety of cytokines/chemokines in epithelial cells and fibroblasts, and induce the recruitment of basophils, T cells, and eosinophils into sites of allergic inflammation as well as their own intraepithelial accumulation....

BackgroundHouse dust mite (HDM) is the major indoor allergen for allergic diseases such as allergic rhinitis (AR) and asthma. Although sublingual immunotherapy is a curative treatment for HDM‐induced AR, data from large‐scale studies are limited. We evaluated the efficacy and safety of HDM tablets in adolescent and adult patients (aged 12–64 years) with HDM‐induced AR with or without intermittent asthma.MethodsIn a double‐blind trial in Japan, 968 subjects were randomized 1 : 1 : 1 to 300 index of reactivity (IR), 500 IR, or placebo groups. The primary endpoint was the Average Adjusted Symptom Score (AASS) in the last eight weeks of the 52‐week treatment. Secondary endpoints included individual nasal and ocular symptom scores, rescue medication use, and the Japanese Rhinoconjunctivitis Quality of Life Questionnaire (JRQLQ) scores.ResultsThe AASS in the last eight weeks of treatment significantly improved in both the 300 IR and the 500 IR groups compared to that in the placebo group (P < 0.001). In the 300 IR group, the onset of action occurred at week 8–10. All four nasal symptoms significantly improved in both active treatment groups; rescue medication use and JRQLQ outcome improved in the 300 IR group. Most adverse events (AEs) were mild, and 16 serious AEs (SAEs) were reported; however, none of them were drug‐related.ConclusionsOne‐year treatment with 300 IR and 500 IR HDM tablets was effective without major safety concerns. The recommended therapeutic dose for AR is 300 IR.