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Your search keyword '"Yoshiya Tsunoda"' showing total 2 results
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2 results on '"Yoshiya Tsunoda"'

1. Has2 Regulates the Development of Ovalbumin-Induced Airway Remodeling and Steroid Insensitivity in Mice

Author

Mingma Thsering Sherpa, Takumi Kiwamoto, Masashi Matsuyama, Yoshiya Tsunoda, Kai Yazaki, Kazufumi Yoshida, Masayuki Nakajima, Yosuke Matsuno, Yuko Morishima, Yukio Ishii, and Nobuyuki Hizawa

Subjects
ER stress response, HAS2, IL-17, TGF-β1, airway remodeling, asthma, Immunologic diseases. Allergy, RC581-607
Abstract

HAS2 is a member of the gene family encoding the hyaluronan synthase 2, which can generate high-molecular-weight hyaluronan (HMW-HA). Our previous study identified HAS2 as a candidate gene for increased susceptibility to adult asthma. However, whether HAS2 dysfunction affects airway remodeling and steroid insensitivity is still limited. Therefore, this study aimed to clarify the Has2 dysfunction, triggering severe airway remodeling and steroid insensitivity in a murine model of asthma. Has2 heterozygous-deficient (Has2+/−) mice and their wild-type littermates have been evaluated in a model of chronic ovalbumin (OVA) sensitization and challenge. Mice present a higher sensitivity to OVA and higher IL-17 release as well as eosinophilic infiltration. RNA sequencing demonstrated the downregulation of EIF2 signaling pathways, TGF-β signaling pathways, and heat shock proteins with Th17 bias in Has2+/−-OVA mice. The combined treatment with anti-IL-17A antibody and dexamethasone reduces steroid insensitivity in Has2+/−-OVA mice. Has2 attenuation worsens eosinophilic airway inflammation, airway remodeling, and steroid insensitivity. These data highlight that HAS2 and HMW-HA are important for controlling intractable eosinophilic airway inflammation and remodeling and could potentially be exploited for their therapeutic benefits in patients with asthma.

Published
2022
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2. ELOVL6 deficiency aggravates allergic airway inflammation through the ceramide-S1P pathway in mice

Author

Kazufumi Yoshida, Yuko Morishima, Satoshi Ano, Hirofumi Sakurai, Kenya Kuramoto, Yoshiya Tsunoda, Kai Yazaki, Masayuki Nakajima, Mingma Thering Sherpa, Masashi Matsuyama, Takumi Kiwamoto, Yosuke Matsuno, Yukio Ishii, Akio Hayashi, Takashi Matsuzaka, Hitoshi Shimano, and Nobuyuki Hizawa

Subjects
Immunology, Immunology and Allergy
Abstract

Elongation of very-long-chain fatty acids protein 6 (ELOVL6), an enzyme regulating elongation of saturated and monounsaturated fatty acids with C12-C16 to those with C18, has been recently indicated to affect various immune and inflammatory responses; however, the precise process by which ELOVL6-related lipid dysregulation affects allergic airway inflammation is unclear.To evaluate the biological roles of ELOVL6 in allergic airway responses and investigate whether regulating lipid composition in the airways could be an alternative treatment for asthma.Expressions of ELOVL6 and other isoforms were examined in the airways of severely asthmatic patients and mouse models of asthma. Wild-type (WT) and ELOVL6-deficient (Elovl6ELOVL6 expression was downregulated in the bronchial epithelium of severely asthmatic patients compared with controls. In asthmatic mice, ELOVL6 deficiency led to enhanced airway inflammation in which lymphocyte egress from lymph nodes was increased, and both type 2 and non-type 2 immune responses were upregulated. Lipidomic profiling revealed that the levels of palmitic acid, ceramides and sphingosine-1-phosphate (S1P) were higher in the lungs of OVA-immunized Elovl6This study illustrates a crucial role for ELOVL6 in controlling allergic airway inflammation via regulation of fatty acid composition and ceramide-S1P biosynthesis, and indicates that ELOVL6 may be a novel therapeutic target for asthma.

Published
2021

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