Pathogenic changes in group 2 innate lymphoid cells (ILC2) in intractable asthma
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- Nabe Takeshi
- Laboratory of Immunopharmacology, Faculty of Pharmaceutical Sciences, Setsunan University
Bibliographic Information
- Other Title
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- 難治性喘息における2型自然リンパ球（ILC2）の病的変化
Abstract
<p>There is a certain population of intractable asthma patients, who can not be controlled by corticosteroid therapy. It has been suggested that 5–10% of asthma patients have been suffered from steroid resistance. Since it has been difficult to develop a steroid-resistant asthma model, the detailed mechanisms have been unclear. Recently, an intractable asthma model showing steroid insensitivity was developed by the author and colleagues. We found that pathogenic changes in type 2 innate lymphoid cells (ILC2) were induced in the intractable asthma. When ovalbumin (OVA) + Al(OH)3-sensitized BALB/c mice were intratracheally challenged with OVA at 5 μg/animal, development of airway remodeling as well as lung eosinophilia and neutrophilia were markedly suppressed by treatment with dexamethasone. In contrast, when increasing the dose of OVA for challenges to 500 μg/animal, those asthmatic responses turned to be steroid insensitive. When Th2 cells and ILC2 in the lung were stimulated in vitro, ILC2 produced larger amounts of type 2 cytokines than Th2 cells. Interestingly, amounts of type 2 cytokines produced by the steroid-insensitive model-derived ILC2 were significantly larger than those by the steroid-sensitive, and that the former ILC2 exhibited higher expression of thymic stromal lymphopoietin (TSLP) receptor and signal transducer and activator of transcription (STAT) 5a gene. Treatment with anti-IL-5 antibody improved the steroid sensitivity. Taken together, ILC2 have been transformed to be pathogenic in the intractable asthma. IL-5 hyper-produced from ILC2 may be involved in the development of steroid resistance. The molecules related to the above mentioned are expected to be targets for development of new therapeutic drugs for intractable asthma.</p>
Journal
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- Folia Pharmacologica Japonica
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Folia Pharmacologica Japonica 157 (5), 299-304, 2022
The Japanese Pharmacological Society