Lysophosphatidic Acid Regulates the Differentiation of Th2 Cells and Its Antagonist Suppresses Allergic Airway Inflammation

• Material Type: 博士論文
• Title: Lysophosphatidic Acid Regulates the Differentiation of Th2 Cells and Its Antagonist Suppresses Allergic Airway Inflammation
• Author/Editor: Kondo, Mayo; Tezuka, Toshifumi; Ogawa, Hirohisa; Koyama, Kazuya; Bando, Hiroki; Azuma, Masahiko; Nishioka, Yasuhiko
• Author Heading: Kondo, Mayo; Tezuka, Toshifumi; Ogawa, Hirohisa; Koyama, Kazuya; Bando, Hiroki; Azuma, Masahiko; Nishioka, Yasuhiko
• Publication, Distribution, etc.: karger
• Publication Date: 2020-08-26
• Publication Date (W3CDTF): 2020-08-26
• Alternative Title: リゾホスファチジン酸はTh2細胞の分化を制御し、その拮抗薬はアレルギー性気道炎症を抑制する; Lysophosphatidic Acid Induces Allergic Inflammation
• Periodical title: International Archives of Allergy and Immunology
• No. or year of volume/issue: 182 1
• Volume: 182
• Issue: 1
• Pages: 1-13
• ISSN (Periodical Title): ISSN : 1018-2438; ISSN : 1423-0097
• Degree grantor/type: 徳島大学
• Date Granted: 2020-10-22
• Dissertation Number: 甲第3463号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Lysophosphatidic acid; LPA2 antagonist; allergic airway inflammation; Th2 cells
• Target Audience: 一般
• Note (General): Background: Lysophosphatidic acid (LPA), a prototypic member of a large family of lysophospholipids, has been recently shown to play a role in immune responses to respiratory diseases. The involvement of LPA in allergic airway inflammation has been reported, but the mechanism remains unclear. Object: We analyzed the biological activity of LPA in vitro and in vivo and investigated its role in allergic inflammation in mice using an LPA receptor 2 (LPA2) antagonist. Methods: We used a murine model with acute allergic inflammation, in which mice are sensitized and challenged with house dust mite, and analyzed airway hyperresponsiveness (AHR), pathological findings, Th2 cytokines, and IL-33 in bronchoalveolar lavage fluid (BALF) and lung homogenates. The effect of LPA on Th2 differentiation and cytokine production was examined in vitro using naive CD4+ T cells isolated from splenocytes. We also investigated in vivo the effects of LPA on intranasal administration in mice. Results: The LPA2 antagonist suppressed the increase of AHR, the number of total cells, and eosinophils in BALF and lung tissue. It also decreased the production of IL-13 in BALF and IL-33 and CCL2 in the lung. LPA promoted Th2 cell differentiation and IL-13 production by Th2 cells in vitro. Nasal administration of LPA significantly increased the number of total cells and IL-13 in BALF via regulating the production of IL-33 and CCL-2-derived infiltrating macrophages. Conclusion: These findings suggest that LPA plays an important role in allergic airway inflammation and that the blockade of LPA2 might have therapeutic potential for bronchial asthma.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): © 2020 S. Karger AG, Basel
• Related Material (DOI): 10.1159/000509804
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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