Language：Japanese   Publisher：(一社)日本衛生学会  

Language：Japanese   Publisher：(一社)日本衛生学会  

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: Histamine derived from mast cells and basophils plays important roles in inducing allergic symptoms. Although T cells also produce histamine, the involvement of the histamine produced from T cells has remained enigmatic. We sought to reveal the roles of T helper 2 (Th2) cell-derived histamine in nasal allergic disorders. METHODS: The histamine production from Th2 cells was measured by EIA. The mRNA expression of histidine decarboxylase (HDC) was measured by real-time PCR. To investigate the roles of Th2 cell-derived histamine in vivo, we analyzed an antigen-specific Th2 cell transfer mouse model. RESULTS: Th2 cells produced histamine by T cell receptor stimulation, and these properties were specific for Th2 cells, but not Th1 cells and naïve CD4 T cells. The histamine produced from Th2 cells was involved in the infiltrations of Th2 cells in response to antigen exposure. CONCLUSION: These results suggest that Th2 cell-derived histamine play important roles in nasal allergic disorders.

DOI： 10.1007/s00011-021-01458-x

PubMed

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Histamine, which is mainly produced by mast cells and basophils, participates in various allergic symptoms, and some studies have reported that macrophages also produce histamine. Moreover, recent studies have revealed that macrophages, especially alternatively activated macrophages (M2) induced by T helper 2 (Th2) cytokines, such as interleukin (IL)-4 and IL-13, participate in the pathogenesis of allergic diseases. The major source of Th2 cytokines is antigen-specific Th2 cells. To elucidate the relationship between histamine, macrophages, and Th2 cells in allergic inflammation, we established a macrophage-Th2 cell co-culture model in vitro and an antigen-specific Th2 cell transfer mouse model of rhinitis. In vitro analyses indicated that macrophages produce histamine by interacting with antigen-specific Th2 cells through the antigen. Furthermore, Th2 cells and macrophages cooperatively elicited rhinitis in the mouse model. We determined that histamine induces Th2- and macrophage-elicited sneezing responses through H1 receptor signaling, whereas it induces nasal eosinophil infiltrations through H4 receptor signaling. Collectively, these results indicate a novel histamine production mechanism by macrophages, in which Th2 cells and macrophages cooperatively induce nasal allergic inflammation through histamine signaling.

DOI： 10.1371/journal.pone.0248158

PubMed

Authorship：Lead author  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

Background: There have been no studies of dual administration of sublingual immunotherapy (SLIT) tablets for perennial and seasonal allergic rhinitis. This trial (JapicCTI-184014) was conducted to investigate the safety profile and immunological response during dual therapy with SQ house dust mite (HDM) and Japanese cedar pollen (JCP) SLIT tablets.Methods: This was a multicenter, open-label, randomized trial of 109 Japanese patients with coexisting HDM and JCP allergic rhinitis who had positive tests for HDM- and JCP specific IgE (>= 0.7 kU/L). Patients were allocated to receive HDM (N = 54) or JCP (N = 55) SLIT tablets alone for 4 weeks followed by 8 weeks of dual therapy with both SLIT tablets administered within 5 min of each other. Adverse events (AEs), adverse drug reactions (ADRs), and serum IgE and IgG4 specific for HDM (Dermatophagoides farinae, Dermatophagoides pteronyssinus) and JCP were recorded.Results: The percentage of subjects with AEs and ADRs was similar between the two groups and between the two periods of monotherapy and dual therapy. Most AEs and ADRs were mild in severity, and no serious events were observed. The most common ADRs were local events in the oral cavity. Levels of IgE and IgG4 specific for HDM (D. farinae, D. pteronyssinus) and JCP were increased after treatment with HDM and JCP SLIT tablets, respectively.Conclusions: Dual therapy with both SLIT tablets administered within 5 min after 4 weeks of monotherapy with HDM or JCP tablet was well tolerated and induced the expected immunological responses. Copyright (C) 2019, Japanese Society of Allergology. Production and hosting by Elsevier B.V.

DOI： 10.1016/j.alit.2019.07.007

Web of Science

Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

Language：Japanese   Publisher：日本小児耳鼻咽喉科学会  

Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

Corticosteroid-resistant ILC2s exacerbate nasal T(h)2 inflammation.Both T(h)2 cells and group 2 innate lymphoid cells (ILC2s) contribute to allergic diseases. However, their exact role and relationship in nasal allergic disorders are unclear. In this study, we investigated the cooperation of T(h)2 cells and ILC2s in a mouse model of nasal allergic disorder. To differentially activate T(h)2 cells and/or ILC2s in nasal mucosa, mice were intra-nasally administered ovalbumin (OVA) antigen, papain, an ILC2-activator, or both for 2 weeks. Epithelial thickness and number of eosinophils in the nasal mucosa were evaluated at 24 h after the final challenge. Intra-nasal administration of OVA and papain preferentially activated T(h)2 cells and ILC2s, respectively, in the nose. Both OVA and papain increased the nasal epithelial thickness and number of eosinophils, and their coadministration significantly enhanced the symptoms. Although T-/B-cell-deficient mice showed severely decreased nasal symptoms induced by OVA or OVA-plus-papain, the mice still showed slight papain-induced nasal symptoms. In ILC2-deficient mice, OVA-plus-papain-induced nasal symptoms were suppressed to the same level as OVA-alone. Similarly, IL-33- and ST2-deficient mice showed decreased OVA-plus-papain-induced nasal symptoms. IL-5 induced eosinophilia only, but IL-13 contributed to both nasal epithelial thickening and eosinophilia induced by OVA-plus-papain. Dexamethasone ameliorated OVA-alone-induced nasal epithelial thickening. However, OVA-plus-papain-induced nasal epithelial thickening was only partially controlled by dexamethasone. These results demonstrate that IL-33/ST2-pathway-mediated ILC2 activation exacerbated T(h)2-cell-induced nasal inflammation by producing IL-13. Although T(h)2-cell-alone-induced nasal inflammation was controlled by corticosteroid treatment, the activation of ILC2s conferred treatment resistance. Therefore, ILC2s and their activators could be therapeutic targets for treatment-refractory nasal allergic disorders.

DOI： 10.1093/intimm/dxx030

Web of Science

PubMed

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

Language：Japanese   Publisher：Japanese Society of Allergology  

DOI： 10.15036/arerugi.66.936

Scopus

PubMed

Authorship：Lead author  

Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

Thymic stromal lymphopoietin (TSLP) and IL-33 are epithelium-derived proallergic cytokines that contribute to allergic diseases. Although the involvement of TSLP in allergic rhinitis (AR) is suggested, the exact role of TSLP in AR is poorly understood. Furthermore, the relative contribution of TSLP and IL-33 in nasal allergic responses has not been described. In this study, we examined the roles of TSLP and IL-33 in AR by analyzing acute and chronic AR models. Acute AR mice were intraperitoneally immunized with ragweed, then intranasally challenged with ragweed pollen for four consecutive days. Chronic AR mice were nasally administrated ragweed pollen on consecutive days for 3 weeks. In both models, TSLP receptor (TSLPR)-deficient mice showed defective sneezing responses and reduced serum ragweed-specific IgE levels compared with wild-type (WT) mice. Analyses of bone-marrow chimeric mice demonstrated that hematopoietic cells were responsible for defective sneezing in TSLPR-deficient mice. In addition, FceRI+-cell-specific TSLPR-deficient mice showed partial but significant reduction in sneezing responses. Of note, T-h2 activation and nasal eosinophilia were comparable between WT and TSLPR-deficient mice. ST2- and IL-33-deficient mice showed defective T-h2 activation and nasal eosinophilia to acute, but not chronic, ragweed exposure. TSLPR and ST2 double-deficient mice showed defective T-h2 activation and nasal eosinophilia even after chronic ragweed exposure. These results demonstrate that TSLPR signaling is critical for the early phase response of AR by controlling the IgE-mast-cell/basophil pathway. The IL-33/ST2 pathway is central to nasal T-h2 activation during acute allergen exposure, but both TSLPR and ST2 contribute to T-h2 responses in chronically allergen-exposed mice.

DOI： 10.1093/intimm/dxv055

Web of Science

PubMed

Language：Japanese   Publisher：(一社)日本アレルギー学会  

Language：Japanese   Publisher：(NPO)日本気管食道科学会  

Language：Japanese   Publisher：日本味と匂学会  

2007年2月から2011年8月に嗅覚外来を受診した190例のうち、先天性嗅覚障害と診断した7例(男3名、女4名、5〜57歳)の臨床的検討を行った。性腺機能不全を合併しKallmann症候群と診断したのは1例のみで、小児2例はKallmann症候群が疑われ、ゴナドトロピン分泌負荷試験を実施予定である。性腺機能不全を伴わない嗅覚障害のみの症例が4例であった。基準嗅力検査は7例中6例が嗅覚脱失、1例が高度嗅覚障害であった。アリナミンテストを実施した6例は全例無反応であった。MRI検査により嗅球、嗅溝を描出することができるが、7例中5例は嗅球が無形成、2例は低形成であった。嗅溝は7例中6例が正常所見で、1例のみ無形成であった。34歳男性、8歳男性症例を提示した。

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2011&ichushi_jid=J04102&link_issn=&doc_id=20120213140084&doc_link_id=%2Fcw7jasts%2F2011%2F001803%2F125%2F0613-0616%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcw7jasts%2F2011%2F001803%2F125%2F0613-0616%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Authorship：Lead author   Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

突発性難聴の経過中に良性発作性頭位めまい症様症候を伴った3症例を報告した。症例1は66歳女性で、右難聴・耳鳴を主訴とした。高血圧症、糖尿病、高コレステロール血症の既往があった。症例2は70歳女性で、右難聴・回転性めまいを主訴とした。高血圧症の既往があった。症例3は31歳女性で、右難聴・回転性めまいを主訴とした。もやもや病の既往があった。全例、外側半規管型結石症を疑ったが、画像所見で器質的異常を認めなかった。ヒドロコルチゾンを点滴投与し、症例1、3では低音域の聴力が1日で劇的に改善した。両例は退院時、高音域の聴力低下が残存していたが、突発性難聴の聴力回復判定基準によれば著明回復および回復であった。症例2は発症5日目に聾型を呈し、以後改善は認めなかった。症例1、2は温度刺激検査で半規管麻痺を認めたが、3ヵ月後には改善していた。全例に理学療法を施行し、症例2、3には効果を認めた。

Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.63.958

CiNii Books