Reassessing the Roles of T Lymphocytes and Mast Cells in the Pathogenesis of Allergic Rhinitis

Pawankar, Ruby Korean Rhinologic Society 1999 Journal of rhinology Vol.6 No.1

Climate Change and Air Pollution: Effects on Respiratory Allergy

Gennaro D’Amato,Ruby Pawankar,Carolina Vitale,Maurizia Lanza,Antonio Molino,Anna Stanziola,Alessandro Sanduzzi,Alessandro Vatrella,Maria D’Amato 대한천식알레르기학회 2016 Allergy, Asthma & Immunology Research Vol.8 No.5

A body of evidence suggests that major changes involving the atmosphere and the climate, including global warming induced by anthropogenic factors, have impact on the biosphere and human environment. Studies on the effects of climate change on respiratory allergy are still lacking and current knowledge is provided by epidemiological and experimental studies on the relationship between allergic respiratory diseases, asthma and environmental factors, such as meteorological variables, airborne allergens, and air pollution. Urbanization with its high levels of vehicle emissions, and a westernized lifestyle are linked to the rising frequency of respiratory allergic diseases and bronchial asthma observed over recent decades in most industrialized countries. However, it is not easy to evaluate the impact of climate changes and air pollution on the prevalence of asthma in the general population and on the timing of asthma exacerbations, although the global rise in asthma prevalence and severity could also be an effect of air pollution and climate change. Since airborne allergens and air pollutants are frequently increased contemporaneously in the atmosphere, an enhanced IgE-mediated response to aeroallergens and enhanced airway inflammation could account for the increasing frequency of respiratory allergy and asthma in atopic subjects in the last 5 decades. Pollen allergy is frequently used to study the relationship between air pollution and respiratory allergic diseases, such as rhinitis and bronchial asthma. Epidemiologic studies have demonstrated that urbanization, high levels of vehicle emissions, and westernized lifestyle are correlated with an increased frequency of respiratory allergy prevalently in people who live in urban areas in comparison with people living in rural areas. Climatic factors (temperature, wind speed, humidity, thunderstorms, etc.) can affect both components (biological and chemical) of this interaction.

Expression and Roles of MMP-2, MMP-9, MMP-13, TIMP-1, and TIMP-2 in Allergic Nasal Mucosa

Sachiko Mori,Ruby Pawankar,Chika Ozu,Manabu Nonaka,Toshiaki Yagi,Kimihiro Okubo 대한천식알레르기학회 2012 Allergy, Asthma & Immunology Research Vol.4 No.4

Purpose: Allergic rhinitis (AR) and asthma share many characteristics, but structural changes are observed far less often in AR. Matrix metalloproteinases (MMPs) constitute a family of Zn-dependent endopeptidases that can decompose the extracellular matrix and basement membrane, and regulate cell infiltration. We analyzed the expression of MMPs and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), in allergic nasal mucosa after nasal allergen challenge (NAC) and determined their relationship to inflammatory cells. Methods: Nasal mucosa specimens were obtained at surgery performed for hypertrophied turbinates. We performed NAC with house dust mite (HDM) allergen disks and control disks, and took biopsies at 30 minutes, 6 hours, and 12 hours after NAC. Cells expressing MMP-2, MMP-9, MMP-13, TIMP-1, and TIMP-2, as well as eosinophils and mast cells, were analyzed immunohistochemically. The MMPs and TIMPs in allergic nasal mucosa were quantified using enzyme-linked immunosorbent assays. Results: At 30 minutes post-NAC, HDM-exposed nasal mucosa exhibited significantly more MMP-2+, MMP-9+, MMP-13+, TIMP-1+, and TIMP-2+ cells compared with control mucosa, and the numbers of MMP-9+ and TIMP-1+ cells correlated strongly with the number of mast cells. At 6 hours post-NAC, the numbers of MMP+ and TIMP+ cells did not differ significantly between HDM-exposed mucosa and control mucosa, but the ratios of MMP+ cells to TIMP+ cells were higher in HDM-exposed mucosa. At 12 hours post-NAC, the number of MMP-13+cells tended to be higher in HDM-exposed mucosa and was strongly correlated with the number of eosinophils. Quantitatively, the levels of MMP-2and MMP-13 were significantly higher than the MMP-9 level, and the TIMP-2 level was significantly higher than the TIMP-1 level in allergic nasal mucosa. Conclusions: We demonstrated increased expression of MMP-2, MMP-9, and MMP-13 in allergic nasal mucosa, high MMPs-to-TIMP-1ratios, and a strong correlation between MMP-9 and mast cells and between MMP-13 and eosinophils. The imbalance between MMPs and TIMPs may contribute to the migration of inflammatory cells such as eosinophils and mast cells to the nasal mucosa of AR patients, suggesting a possible active role of MMPs in AR.

Increased Expression and Role of Thymic Stromal Lymphopoietin in Nasal Polyposis

Satoko Kimura,Ruby Pawankar,Sachiko Mori,Manabu Nonaka,Satoru Masuno,Toshiaki Yagi,Kimihiro Okubo 대한천식알레르기학회 2011 Allergy, Asthma & Immunology Research Vol.3 No.3

Purpose: Nasal polyposis is a chronic inflammatory disease of the upper airways often associated with asthma and characterized by markedly increased numbers of eosinophils, Th2 type lymphocytes, fibroblasts, goblet cells and mast cells. Previous studies have shown elevated levels of thymic stromal lymphopoietin (TSLP) in atopic diseases like asthma, atopic dermatitis and mainly in animal models of allergic rhinitis (AR). Here, we investigated the expression of TSLP in nasal polyps from atopics and non-atopics in comparison with the nasal mucosa and its potential role in nasal polyposis. Methods: Messenger RNA expression for TSLP, thymus and activation-regulated chemokine (TARC) and macrophage derived chemokine (MDC) in nasal polyps and nasal mucosa of atopics and non-atopics was analyzed by real time PCR. Immunoreactivity for TSLP in nasal polyps and in the nasal mucosa of patients with AR and non-allergic rhinitis (NAR) was analyzed by immunohistochemistry. Eosinophil counts was analyzed by Wright-Giemsa staining and nasal polyp tissue IgE, by ELISA. Results: Messenger RNA expression for TSLP,TARC and MDC was markedly higher in nasal polyps as compared to the allergic nasal mucosa. Immunoreactivity for TSLP was detected in epithelial cells, endothelial cells, fibroblasts and inflammatory cells of the nasal mucosa and nasal polyps. The number of TSLP+ cells was significantly greater in the nasal mucosa of AR than NAR patients. The number of TSLP+ cells in nasal polyps from atopics was significantly greater than that of non-atopics and that in the allergic nasal mucosa. The number of TSLP+ cells correlated well with the number of eosinophils and the levels of IgE in nasal polyps. Conclusions: The high expression of TSLP in nasal polyps and its strong correlation to eosinophils and IgE suggest a potential role for TSLP in the pathogenesis of nasal polyps by regulating the Th2 type and eosinophilic inflammation.

Decreased Expression of FOXP3 in Nasal Polyposis

Kannika Roongrotwattanasiri,Ruby Pawankar,Satoko Kimura,Sachiko Mori,Manabu Nonaka,Toshiaki Yagi 대한천식알레르기학회 2012 Allergy, Asthma & Immunology Research Vol.4 No.1

Purpose: The pathogenesis of nasal polyposis (NP) is unclear. Eosinophils and mast cells are considered to play important roles in this process. In addition, the levels of Th2-type cells are increased, irrespective of the atopic status of the patient with NP. In this context, we and others have shown high levels of thymus and activation-related chemokine/CCL17, macrophage-derived chemokine, eotaxin, and RANTES in patients with NP. Forkhead box P3 (FOXP3) plays a key role in CD4+CD25+ regulatory T-cell function and represents a specific marker for regulatory T cells (Tregs). Decreased expression of FOXP3 has been reported in allergic diseases. The present study was designed to evaluate the presence and potential roles of Tregs, defined by the expression of FOXP3 protein, in NP. Methods: Using immunohistochemistry, we estimated the numbers of FOXP3+ cells in the epithelium and lamina propria of the NPs of 17 patients with chronic rhinosinusitis with NP and the nasal mucosa of 15 patients with allergic rhinitis (AR). The number of FOXP3+ cells in NPs was compared with that in the nasal mucosa of patients with AR, and the numbers of FOXP3+ cells in atopic and non-atopic NP were also compared. Results: The number of FOXP3+ cells in the lamina propria of patients with NP was significantly lower than that in the nasal mucosa of the AR patients (2.79 vs. 5.99, P=0.008). There was no statistically significant difference noted for the numbers of FOXP3+ cells between the epithelium of the NP and the nasal mucosa (3.60 vs. 2.39, P=0.180). Furthermore, the numbers of CD4+FOXP3+cells were lower in NPs than in the allergic nasal mucosa. There was no difference in the number of FOXP3+ cells between the atopic and non-atopic NP patients. Conclusions: Fewer Tregs (i.e., decreased FOXP3 expression) are found in NPs than in the nasal mucosa of AR patients. As the severity of eosinophilic, Th2-type inflammation and the levels of inflammatory mediators are much higher in NPs than in the nasal mucosa of AR patients, an inverse co-relationship may exist between these parameters and the number of Tregs. The deficiency of Tregs in NP may account for the more pronounced Th2-type inflammation seen in these patients.

Improvement of Eosinophilic Otitis Media by Optimized Asthma Treatment

Yukako Tanaka,Yukie Yamamura,Etsuko Tagaya,Ruby Pawankar,Toshio Yoshihara,Manabu Nonaka 대한천식알레르기학회 2013 Allergy, Asthma & Immunology Research Vol.5 No.3

Eosinophilic otitis media (EOM) shows a very high rate of association with asthma, and intractable otitis media involves marked eosinophil infiltration into the middle ear. The middle ear space is connected to the nasopharynx by the Eustachian tube, and it is considered a part of the upper respiratory tract. Allergic rhinitis and asthma often coexist as chronic inflammatory diseases of the upper and lower airways, respectively, and have an impact on each other. In fact, inhaled corticosteroids reduce seasonal eosinophilia systemically in the circulation and locally in the nasal mucosa, as well as attenuate seasonal nasal symptoms. We report a case of EOM associated with adult-onset asthma that improved following optimal asthma therapy after changing the treatment from inhaled fluticasone propionate (FP) (200 µg b.i.d.) to a combination of FP/salmeterol (250/50 µg b.i.d.). This result supports the hypothesis that EOM and asthma are closely linked, presenting as different manifestations of a similar disease syndrome.