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Copyright of Folia Pharmacologica Japonica is the property of Japanese Pharmacological Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Folia Pharmacologica Japonica is the property of Japanese Pharmacological Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Tezepelumab (TEZSPIRE ® Subcutaneous Injection 210 ‍mg), a biologic medicine with a novel mechanism, was approved in Japan in September 2022 for the treatment of bronchial asthma. Tezespire auto-injector was approved in Japan in August 2023 as an additional dosage. It is indicated for severe or refractory patients whose asthmatic symptoms cannot be controlled by currently available treatment. Tezepelumab binds to the epithelial cytokine thymic stromal lymphopoietin (TSLP) and disrupts TSLP signaling via the heterodimeric receptor. In the Phase 3 NAVIGATOR trial, the annual asthma exacerbation rate was significantly reduced by tezepelumab when administered subcutaneously every 4 weeks over a 52-week period to patients with uncontrolled, severe asthma who had received medium- or high-dose inhaled glucocorticoids. Its efficacy in reducing asthma exacerbations was observed regardless of blood eosinophil (bEOS) count, fractional exhaled nitric oxide (FeNO) levels, or serum total IgE at baseline. Significant improvements were noted in lung function, health-related quality of life, and change from baseline in asthma control. Reductions in the levels of inflammatory biomarkers (bEOS, FeNO, and IgE) was also noted. Clinical pharmacology trials demonstrated the efficacy of tezepelumab in improving airway hyperresponsiveness. In this article, we reviewed pharmacological characteristics, pharmacokinetics, clinical efficacy, and the safety profile of tezepelumab.

Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived immunostimulatory factor, which activates several immune cells such as dendritic cells, T cells, and mast cells. Recently, epithelial cell-derived TSLP has gained immense attention as a cytokine that induces allergic immune responses. Therefore, understanding the regulation of TSLP production is an important step in uncovering the pathophysiology of allergic diseases. Moreover, the compounds that regulate TSLP production can be used as therapeutic drugs for the treatment of allergic diseases. We aim to elucidate the detailed regulation of TSLP production from epithelial cells, and in doing so discovered new regulating factors and an inhibitor of TSLP production. This review article explains the role of TSLP in allergic diseases, its regulation, and our research results.

Introduction: We have previously reported that a distinct sensitization pattern was associated with thymic stromal lymphopoietin (TSLP) genotype. The aim of this study is to identify the characteristics of asthma phenotypes determined by a cluster analysis of IgE responsiveness and the relationship between these phenotypes and TSLP genotypes., Patients and Methods: We studied 297 patients of adult asthma and 1571 non-asthmatic healthy adults from Ibaraki, a prefecture in central Japan and Kamishihoro, a cedar-free, birch-dominant town in northern Japan. Levels of total serum IgE and specific IgE antibodies towards 14 major inhaled allergens were measured. With the use of these measures, cluster analysis was applied to classify the phenotypes of adult asthma. We also examined the genetic effects of 2 TSLP functional single nucleotide polymorphism (SNPs) on the development of each asthma phenotype using multinomial logistic regression analysis., Results: The cluster analysis identified four distinct clinical phenotypes of asthma, including "Dust mite dominant" (A, N=82), "Multiple pollen" (B, N=14), "Cedar dominant" (C, N=44), and "Low reactivity" (D, N=154). Asthma phenotype A consisted of younger patients with elevated IgE levels and decreased pulmonary function. Asthma phenotype B was characterized by sensitization by many pollen allergens. Asthma phenotype C was not formed in Kamishihoro. Asthma phenotype D was a group of older women who are less atopic. In current or past smokers, both TSLP SNPs (rs2289276 and rs3860933) were associated with the asthma phenotype D (odds ratio 2.11 [1.36-3.30] and 2.11 [1.34-3.33], respectively)., Conclusion: In patients with adult asthma who are less atopic, the genetic polymorphisms of TSLP may have some important roles in the development of the disease in smokers.