Th9 cells induce steroid-resistant bronchial hyperresponsiveness in mice

• Saeki Mayumi

  Allergy and Immunology Project, Tokyo Metropolitan Institute of Medical Science

• Kaminuma Osamu

  Center for Life Science Research, University of Yamanashi

• Nishimura Tomoe

  Allergy and Immunology Project, Tokyo Metropolitan Institute of Medical Science

• Kitamura Noriko

  Allergy and Immunology Project, Tokyo Metropolitan Institute of Medical Science

• Mori Akio

  Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital

• Hiroi Takachika

  Allergy and Immunology Project, Tokyo Metropolitan Institute of Medical Science

抄録

Background: Reduced responsiveness to corticosteroid therapy is a major problem for patients with severe asthma. Although Th9 cells, along with Th2 cells, facilitate antigen-induced airway eosinophilia and bronchial hyperresponsiveness (BHR), the sensitivity of Th9 cell-mediated responses to steroid therapy remains unknown. In this study, we investigated the effect of dexamethasone (Dex) on antigen-induced airway inflammation in Th9 cell-transferred mice. Methods: Ovalbumin (OVA)-specific Th2 and Th9 cells were polarized from the CD4⁺ T cells of DO11.10/RAG-2^−/− mice. BALB/c mice were adoptively transferred with Th2 or Th9 cells and challenged with OVA. Dex treatment was performed twice, at 1 h before and at 24 h after the OVA challenge. Following treatment, the number of inflammatory cells in the bronchoalveolar lavage fluid and the bronchial responsiveness to inhaled methacholine were determined. Results: In both the Th2 and Th9 cell-transferred mice, substantial accumulation of eosinophils in the lungs and BHR were induced by challenge with the specific antigen. In the Th2 cell-transferred mice, these responses were significantly diminished by Dex treatment. In contrast, neither cellular infiltration nor BHR was affected by Dex treatment in the Th9 cell-transferred mice, although the Th9 cells substantially expressed glucocorticoid receptor α. Accordingly, antigen-induced interleukin-9 expression in the Th9 cells was attenuated by Dex treatment at least in vitro. Antigen-induced lung infiltration of infused Th2 cells but not Th9 cells was significantly suppressed by Dex. Conclusions: In contrast to Th2-mediated responses, Th9-mediated airway inflammation was not affected by Dex. Th9 cells might be involved in the developmental mechanisms of steroid-resistant asthma.

収録刊行物

• Allergology International

  Allergology International 66 (Supplement.1), S35-S40, 2017

  一般社団法人日本アレルギー学会

キーワード

• Airway inflammation
• Bronchial asthma
• Bronchial hyperresponsiveness
• Dexamethasone
• Th9 cells

詳細情報

• CRID: 1390282679611157888
• NII論文ID: 130006182293
• DOI: 10.1016/j.alit.2017.07.001
• ISSN: 14401592
• ISSN: 13238930
• Web Site: https://api.elsevier.com/content/article/PII:S1323893017301028?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S1323893017301028?httpAccept=text/plain
• 本文言語コード: en
• データソース種別:
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