Yasutaka Yun1, Akira Kanda2, Yoshiki Kobayashi3, Dan Van Bui4, Kensuke Suzuki4, Shunsuke Sawada4, Kazuyasu Baba1, Masao Yagi4, Mikiya Asako3, Haruka Okazaki5, Hiroki Ikeda6, Shigeki Kawamura7, Akihiko Nakamura8, David Dombrowicz9, Koichi Tomoda4, Hiroshi Iwai4. 1. Department of Otorhinolaryngology, Head & Neck Surgery, Kansai Medical University, Osaka, Japan; Department of Otorhinolaryngology, Takeda General Hospital, Kyoto, Japan. 2. Department of Otorhinolaryngology, Head & Neck Surgery, Kansai Medical University, Osaka, Japan; Allergy Center, Kansai Medical University, Osaka, Japan. Electronic address: akanda@hirakata.kmu.ca.jp. 3. Department of Otorhinolaryngology, Head & Neck Surgery, Kansai Medical University, Osaka, Japan; Allergy Center, Kansai Medical University, Osaka, Japan. 4. Department of Otorhinolaryngology, Head & Neck Surgery, Kansai Medical University, Osaka, Japan. 5. Okazaki ENT Clinic, Osaka, Japan. 6. Ikeda ENT Clinic, Wakayama, Japan. 7. Kawamura ENT Clinic, Osaka, Japan. 8. Nakamura ENT Clinic, Osaka, Japan. 9. University of Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, Lille, France.
Abstract
BACKGROUND: Eosinophilic chronic rhinosinusitis (ECRS) is a subtype of chronic rhinosinusitis associated with asthma. CD69 is an important marker of activation for eosinophils. But, whether a correlation exist between the CD69 expression on eosinophils and clinical findings is unclear. METHODS: We performed quantitative PCR and/or flow cytometry using tissue and purified eosinophils from the blood and nasal polyps of 12 patients with ECRS and from 8 patients without ECRS (controls). We assessed clinical findings including nasal polyp (NP) scores, sinus CT findings, and pulmonary function test results, and examined their possible association with the CD69 expression. We also performed CD69 cross-linking experiments in mouse eosinophils to investigate the functional role of CD69. RESULTS: Levels of cytokine mRNAs (IL-4, -5, -10, and -13) were significantly higher in purified NP eosinophils and tissues from patients with ECRS than the levels of those in controls. The expressions of major basic protein (MBP), eosinophilic cationic protein (ECP), eosinophilic-derived neurotoxin (EDN), eosinophil peroxidase (EPX) in cytotoxic granules, and CD69 mRNA were significantly higher in purified eosinophils from NPs than in those from blood. We also found a correlation between expression of CD69 and clinical findings. Moreover, we found EPX release from mouse eosinophils following CD69 cross-linking. CONCLUSIONS: These data suggest that increased CD69 expression by eosinophils is not only a biomarker for nasal obstruction and pulmonary dysfunction, but also a potential therapeutic target for patients with ECRS and asthma.
BACKGROUND:Eosinophilic chronic rhinosinusitis (ECRS) is a subtype of chronic rhinosinusitis associated with asthma. CD69 is an important marker of activation for eosinophils. But, whether a correlation exist between the CD69 expression on eosinophils and clinical findings is unclear. METHODS: We performed quantitative PCR and/or flow cytometry using tissue and purified eosinophils from the blood and nasal polyps of 12 patients with ECRS and from 8 patients without ECRS (controls). We assessed clinical findings including nasal polyp (NP) scores, sinus CT findings, and pulmonary function test results, and examined their possible association with the CD69 expression. We also performed CD69 cross-linking experiments in mouse eosinophils to investigate the functional role of CD69. RESULTS: Levels of cytokine mRNAs (IL-4, -5, -10, and -13) were significantly higher in purified NP eosinophils and tissues from patients with ECRS than the levels of those in controls. The expressions of major basic protein (MBP), eosinophilic cationic protein (ECP), eosinophilic-derived neurotoxin (EDN), eosinophil peroxidase (EPX) in cytotoxic granules, and CD69 mRNA were significantly higher in purified eosinophils from NPs than in those from blood. We also found a correlation between expression of CD69 and clinical findings. Moreover, we found EPX release from mouse eosinophils following CD69 cross-linking. CONCLUSIONS: These data suggest that increased CD69 expression by eosinophils is not only a biomarker for nasal obstruction and pulmonary dysfunction, but also a potential therapeutic target for patients with ECRS and asthma.
Authors: Elizabeth A Jacobsen; David J Jackson; Enrico Heffler; Sameer K Mathur; Albert J Bredenoord; Ian D Pavord; Praveen Akuthota; Florence Roufosse; Marc E Rothenberg Journal: Annu Rev Immunol Date: 2021-03-01 Impact factor: 28.527