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：English   Publishing type：Research paper (scientific journal)   Publisher：MOSBY-ELSEVIER  

Background: Allergen-mediated cross-linking of IgE on mast cells/basophils is a well-recognized trigger for type 1 allergic diseases such as allergic rhinitis (AR). However, allergens may not be the sole trigger for AR, and several allergic-like reactions are induced by non-IgE-mediated mechanisms. Objective: We sought to describe a novel non-IgE-mediated, endotoxin-triggered nasal type-1-hypersensitivity-like reaction in mice.
Methods: To investigate whether endotoxin affects sneezing responses, mice were intraperitoneally immunized with ovalbumin (OVA), then nasally challenged with endotoxin-free or endotoxin-containing OVA. To investigate the role of T cells and mechanisms of the endotoxin-induced response, mice were adoptively transferred with in vitro-differentiated OVA-specific T(H)2 cells, then nasally challenged with endotoxin-free or endotoxin-containing OVA.
Results: Endotoxin-containing, but not endotoxin-free, OVA elicited sneezing responses in mice independent from IgE-mediated signaling. OVA-specific T(H)2 cell adoptive transfer to mice demonstrated that local activation of antigen-specific T(H)2 cells was required for the response. The Toll-like receptor 4-myeloid differentiation factor 88 signaling pathway was indispensable for endotoxin-containing OVA-elicited rhinitis. In addition, LPS directly triggered sneezing responses in OVA-specific T(H)2-transferred and nasally endotoxin-free OVA-primed mice. Although antihistamines suppressed sneezing responses, mast-cell/basophil-depleted mice had normal sneezing responses to endotoxin-containing OVA. Clodronate treatment abrogated endotoxin-containing OVA-elicited rhinitis, suggesting the involvement of monocytes/ macrophages in this response.
Conclusions: Antigen-specific nasal activation of CD4 1 T cells followed by endotoxin exposure induces mast cell/basophilindependent histamine release in the nose that elicits sneezing responses. Thus, environmental or nasal residential bacteria may exacerbate AR symptoms. In addition, this novel phenomenon might explain currently unknown mechanisms in allergic(-like) disorders.

DOI： 10.1016/j.jaci.2016.03.023

Web of Science

PubMed

Language：Japanese   Publisher：Japanese Society of Allergology  

DOI： 10.15036/arerugi.66.936

Scopus

PubMed

Authorship：Lead author  

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：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

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

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