好酸球性副鼻腔炎における活性化好酸球の役割
好酸球性副鼻腔炎（Eosinophilic chronic rhinosinusitis: ECRS）は，高頻度に喘息を合併する難治性の慢性副鼻腔炎であり，上下気道にわたる好酸球性気道炎症である．炎症局所に浸潤している組織好酸球は，活性化し病態形成に重要な役割を果たしている．好酸球の活性化マーカーとしてCD69分子が知られているが，CD69分子の機能的役割は，十分に解明されていない．そのため我々は，好酸球性副鼻腔炎患者の組織から好酸球を単離し，好酸球の活性化とCD69の発現の相関およびその機能的役割の解明をおこなった．結果，CD69分子がヒト末梢血好酸球に比較して組織好酸球に高く発現し，CD6...
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| Published in | 関西医科大学雑誌 Vol. 72; pp. 17 - 21 |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
関西医科大学医学会
2021
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0022-8400 2185-3851 |
| DOI | 10.5361/jkmu.72.17 |
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| Abstract | 好酸球性副鼻腔炎（Eosinophilic chronic rhinosinusitis: ECRS）は，高頻度に喘息を合併する難治性の慢性副鼻腔炎であり，上下気道にわたる好酸球性気道炎症である．炎症局所に浸潤している組織好酸球は，活性化し病態形成に重要な役割を果たしている．好酸球の活性化マーカーとしてCD69分子が知られているが，CD69分子の機能的役割は，十分に解明されていない．そのため我々は，好酸球性副鼻腔炎患者の組織から好酸球を単離し，好酸球の活性化とCD69の発現の相関およびその機能的役割の解明をおこなった．結果，CD69分子がヒト末梢血好酸球に比較して組織好酸球に高く発現し，CD69の発現量が症状の重症度と相関していることを明らかにした．さらには，CD69の刺激により好酸球性特異的組織傷害性タンパク質の一種であるEPX（Eosinophilic Peroxidase）を放出することを明らかにした．このことより好酸球性副鼻腔炎に対して，CD69分子は新たな治療戦略のターゲットとなることが期待される． |
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| AbstractList | 好酸球性副鼻腔炎（Eosinophilic chronic rhinosinusitis: ECRS）は，高頻度に喘息を合併する難治性の慢性副鼻腔炎であり，上下気道にわたる好酸球性気道炎症である．炎症局所に浸潤している組織好酸球は，活性化し病態形成に重要な役割を果たしている．好酸球の活性化マーカーとしてCD69分子が知られているが，CD69分子の機能的役割は，十分に解明されていない．そのため我々は，好酸球性副鼻腔炎患者の組織から好酸球を単離し，好酸球の活性化とCD69の発現の相関およびその機能的役割の解明をおこなった．結果，CD69分子がヒト末梢血好酸球に比較して組織好酸球に高く発現し，CD69の発現量が症状の重症度と相関していることを明らかにした．さらには，CD69の刺激により好酸球性特異的組織傷害性タンパク質の一種であるEPX（Eosinophilic Peroxidase）を放出することを明らかにした．このことより好酸球性副鼻腔炎に対して，CD69分子は新たな治療戦略のターゲットとなることが期待される． |
| Author | 神田, 晃 鈴木, 健介 尹, 泰貴 朝子, 幹也 小林, 良樹 岩井, 大 三谷, 彰敏 |
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| References | 4. Rosenberg HF, Dyer KD, Foster PS. Eosinophils: changing perspectives in health and disease. Nat Rev Immunol 13: 9–22, 2013. 12. Shah SA, Ishinaga H, Takeuchi K. Pathogenesis of eosinophilic chronic rhinosinusitis. J Inflamm (Lond) 13: 11, 2016. 16. Ochkur SI, Doyle AD, Jacobsen EA, LeSuer WE, Li W, Protheroe CA, Zellner KR, Colbert D, Shen HH, Irvin CG, Lee JJ, Lee NA. Frontline science: eosinophil-deficient MBP-1 and EPX double-knockout mice link pulmonary remodeling and airway dysfunction with type 2 inflammation. J Leukoc Biol 102: 589–599, 2017. 10. Tanaka S, Hirota T, Kamijo A, Ishii H, Hatsushika K, Fujieda S, Ishitoya J, Masuyama K, Tamari M. Lung functions of Japanese patients with chronic rhinosinusitis who underwent endoscopic sinus surgery. Allergol Int 63: 27–35, 2014. 9. Fujieda S, Imoto Y, Kato Y, Ninomiya T, Tokunaga T, Tsutsumiuchi T, Yoshida K, Kidoguchi M, Takabayashi T. Eosinophilic chronic rhinosinusitis. Allergol Int 2019. 3. Kanda A, Yun Y, Bui DV, Nguyen LM, Kobayashi Y, Suzuki K, Mitani A, Sawada S, Hamada S, Asako M, Iwai H. The multiple functions and subpopulations of eosinophils in tissues under steady-state and pathological conditions. Allergol Int 70: 9–18, 2021. 5. Acharya KR, Ackerman SJ. Eosinophil granule proteins: form and function. J Biol Chem 289: 17406–17415, 2014. 13. Cibrian D, Sanchez-Madrid F. CD69: from activation marker to metabolic gatekeeper. Eur J Immunol 47: 946–953, 2017. 17. Wang HY, Dai Y, Wang JL, Yang XY, Jiang XG. Anti-CD69 monoclonal antibody treatment inhibits airway inflammation in a mouse model of asthma. Journal of Zhejiang University Science B 16: 622–631, 2015. 2. Tokunaga T, Sakashita M, Haruna T, Asaka D, Takeno S, Ikeda H, Nakayama T, Seki N, Ito S, Murata J, Sakuma Y, Yoshida N, Terada T, Morikura I, Sakaida H, Kondo K, Teraguchi K, Okano M, Otori N, Yoshikawa M, Hirakawa K, Haruna S, Himi T, Ikeda K, Ishitoya J, Iino Y, Kawata R, Kawauchi H, Kobayashi M, Yamasoba T, Miwa T, Urashima M, Tamari M, Noguchi E, Ninomiya T, Imoto Y, Morikawa T, Tomita K, Takabayashi T, Fujieda S. Novel scoring system and algorithm for classifying chronic rhinosinusitis: the JESREC Study. Allergy 70: 995–1003, 2015. 11. Uraguchi K, Kariya S, Makihara S, Okano M, Haruna T, Oka A, Fujiwara R, Noda Y, Nishizaki K. Pulmonary function in patients with eosinophilic chronic rhinosinusitis. Auris Nasus Larynx 45: 476–481, 2018. 7. Jacobsen EA, Jackson DJ, Heffler E, Mathur SK, Bredenoord AJ, Pavord ID, Akuthota P, Roufosse F, Rothenberg ME. Eosinophil knockout humans: uncovering the role of eosinophils through eosinophil-directed biological therapies. Annu Rev Immunol 2021. 14. Kimura MY, Hayashizaki K, Tokoyoda K, Takamura S, Motohashi S, Nakayama T. Crucial role for CD69 in allergic inflammatory responses: CD69-Myl9 system in the pathogenesis of airway inflammation. Immunol Rev 278: 87–100, 2017. 8. 間島 雄．慢性鼻副鼻腔炎の成因・診断・治療．耳鼻咽喉科展望 55: 118–125, 2012. 15. Walsh GM, Symon FA, Willars GB, Wardlaw AJ. Ligation of CD69 induces apoptosis and cell death in human eosinophils cultured with granulocyte-macrophage colony-stimulating factor. Blood 87: 2815–2821, 1996. 1. Ishitoya J, Sakuma Y, Tsukuda M. Eosinophilic Chronic Rhinosinusitis in Japan. Allergology International 59: 239–245, 2010. 6. Kanda A, Yasutaka Y, Van Bui D, Suzuki K, Sawada S, Kobayashi Y, Asako M, Iwai H. Multiple biological aspects of eosinophils in host defense, eosinophil-associated diseases, immunoregulation, and homeostasis: is their role beneficial, detrimental, regulator, or bystander? Biological and Pharmaceutical Bulletin 43: 20–30, 2020. |
| References_xml | – reference: 2. Tokunaga T, Sakashita M, Haruna T, Asaka D, Takeno S, Ikeda H, Nakayama T, Seki N, Ito S, Murata J, Sakuma Y, Yoshida N, Terada T, Morikura I, Sakaida H, Kondo K, Teraguchi K, Okano M, Otori N, Yoshikawa M, Hirakawa K, Haruna S, Himi T, Ikeda K, Ishitoya J, Iino Y, Kawata R, Kawauchi H, Kobayashi M, Yamasoba T, Miwa T, Urashima M, Tamari M, Noguchi E, Ninomiya T, Imoto Y, Morikawa T, Tomita K, Takabayashi T, Fujieda S. Novel scoring system and algorithm for classifying chronic rhinosinusitis: the JESREC Study. Allergy 70: 995–1003, 2015. – reference: 12. Shah SA, Ishinaga H, Takeuchi K. Pathogenesis of eosinophilic chronic rhinosinusitis. J Inflamm (Lond) 13: 11, 2016. – reference: 14. Kimura MY, Hayashizaki K, Tokoyoda K, Takamura S, Motohashi S, Nakayama T. Crucial role for CD69 in allergic inflammatory responses: CD69-Myl9 system in the pathogenesis of airway inflammation. Immunol Rev 278: 87–100, 2017. – reference: 3. Kanda A, Yun Y, Bui DV, Nguyen LM, Kobayashi Y, Suzuki K, Mitani A, Sawada S, Hamada S, Asako M, Iwai H. The multiple functions and subpopulations of eosinophils in tissues under steady-state and pathological conditions. Allergol Int 70: 9–18, 2021. – reference: 6. Kanda A, Yasutaka Y, Van Bui D, Suzuki K, Sawada S, Kobayashi Y, Asako M, Iwai H. Multiple biological aspects of eosinophils in host defense, eosinophil-associated diseases, immunoregulation, and homeostasis: is their role beneficial, detrimental, regulator, or bystander? Biological and Pharmaceutical Bulletin 43: 20–30, 2020. – reference: 16. Ochkur SI, Doyle AD, Jacobsen EA, LeSuer WE, Li W, Protheroe CA, Zellner KR, Colbert D, Shen HH, Irvin CG, Lee JJ, Lee NA. Frontline science: eosinophil-deficient MBP-1 and EPX double-knockout mice link pulmonary remodeling and airway dysfunction with type 2 inflammation. J Leukoc Biol 102: 589–599, 2017. – reference: 7. Jacobsen EA, Jackson DJ, Heffler E, Mathur SK, Bredenoord AJ, Pavord ID, Akuthota P, Roufosse F, Rothenberg ME. Eosinophil knockout humans: uncovering the role of eosinophils through eosinophil-directed biological therapies. Annu Rev Immunol 2021. – reference: 10. Tanaka S, Hirota T, Kamijo A, Ishii H, Hatsushika K, Fujieda S, Ishitoya J, Masuyama K, Tamari M. Lung functions of Japanese patients with chronic rhinosinusitis who underwent endoscopic sinus surgery. Allergol Int 63: 27–35, 2014. – reference: 1. Ishitoya J, Sakuma Y, Tsukuda M. Eosinophilic Chronic Rhinosinusitis in Japan. Allergology International 59: 239–245, 2010. – reference: 9. Fujieda S, Imoto Y, Kato Y, Ninomiya T, Tokunaga T, Tsutsumiuchi T, Yoshida K, Kidoguchi M, Takabayashi T. Eosinophilic chronic rhinosinusitis. Allergol Int 2019. – reference: 13. Cibrian D, Sanchez-Madrid F. CD69: from activation marker to metabolic gatekeeper. Eur J Immunol 47: 946–953, 2017. – reference: 5. Acharya KR, Ackerman SJ. Eosinophil granule proteins: form and function. J Biol Chem 289: 17406–17415, 2014. – reference: 8. 間島 雄．慢性鼻副鼻腔炎の成因・診断・治療．耳鼻咽喉科展望 55: 118–125, 2012. – reference: 17. Wang HY, Dai Y, Wang JL, Yang XY, Jiang XG. Anti-CD69 monoclonal antibody treatment inhibits airway inflammation in a mouse model of asthma. Journal of Zhejiang University Science B 16: 622–631, 2015. – reference: 4. Rosenberg HF, Dyer KD, Foster PS. Eosinophils: changing perspectives in health and disease. Nat Rev Immunol 13: 9–22, 2013. – reference: 15. Walsh GM, Symon FA, Willars GB, Wardlaw AJ. Ligation of CD69 induces apoptosis and cell death in human eosinophils cultured with granulocyte-macrophage colony-stimulating factor. Blood 87: 2815–2821, 1996. – reference: 11. Uraguchi K, Kariya S, Makihara S, Okano M, Haruna T, Oka A, Fujiwara R, Noda Y, Nishizaki K. Pulmonary function in patients with eosinophilic chronic rhinosinusitis. Auris Nasus Larynx 45: 476–481, 2018. |
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| Snippet | 好酸球性副鼻腔炎（Eosinophilic chronic rhinosinusitis: ECRS）は，高頻度に喘息を合併する難治性の慢性副鼻腔炎であり，上下気道にわたる好酸球性気道炎症である．炎症... |
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| SubjectTerms | CD69 eosinophilic peroxidase 好酸球 好酸球性副鼻腔炎 鼻茸 |
| Title | 好酸球性副鼻腔炎における活性化好酸球の役割 |
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