Geoffrey Mortuaire1, Isabelle Gengler2, Claire Vandenhende-Szymanski2, Marie Delbeke3, Solène Gatault3, Dominique Chevalier4, Lionel Prin5, Monique Capron3. 1. INSERM U995, Université de Lille, Lille, France; EA 2686, Université de Lille, Lille, France; Department of Otorhinolaryngology-Head and Neck Surgery, University Hospital, Lille, France; French Eosinophil Network, University Hospital, Lille, France. Electronic address: g-mortuaire@chru-lille.fr. 2. INSERM U995, Université de Lille, Lille, France; Department of Otorhinolaryngology-Head and Neck Surgery, University Hospital, Lille, France. 3. INSERM U995, Université de Lille, Lille, France. 4. Department of Otorhinolaryngology-Head and Neck Surgery, University Hospital, Lille, France. 5. EA 2686, Université de Lille, Lille, France; French Eosinophil Network, University Hospital, Lille, France.
Abstract
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is frequently associated with asthma. Mucosal eosinophil (EO) infiltrate has been found to correlate with asthma and disease severity but not necessarily in every patient. Other multifactorial immune processes are required to determine disease endotypes and response to treatment. OBJECTIVE: To evaluate EO immunomodulation for migration and survival in accordance with inflammatory protein profiles and asthmatic status in CRSwNP. METHODS: Ninety-three patients (47 with asthma) with CRSwNP were included. Each patient was staged clinically according to symptom severity and polyp size. Nasal secretions were collected to establish a cytokine profile. The EOs were purified from blood samples and nasal polyps to delineate specific immunophenotypes by flow cytometry and determine in vitro EO survival in relation to asthmatic status. RESULTS: The CRSwNP in patients with asthma was characterized by eosinophilia and a high level of interleukin (IL)-5 in nasal secretions. Although EOs exhibited activation profiles after mucosal migration, there was relative down-expression of IL-5 receptor-α (IL-5Rα) on nasal EOs in patients with asthma. The EO culture with IL-5 and IL-9 showed an antiapoptotic effect in patients with asthma through IL-5Rα modulation. CONCLUSION: Mucosal eosinophilia seems to be induced by EO nasal trapping through modulation of adhesion receptors. In patients with asthma, EO involvement is enhanced by the antiapoptotic synergistic action of T-helper cell type 2 cytokines on IL-5Rα expression. This study shows for the first time that IL-9 is involved in EO homeostasis in CRSwNP and could explain the low benefit of anti-IL-5 therapy for some patients with asthma and nasal polyposis.
BACKGROUND:Chronic rhinosinusitis with nasal polyps (CRSwNP) is frequently associated with asthma. Mucosal eosinophil (EO) infiltrate has been found to correlate with asthma and disease severity but not necessarily in every patient. Other multifactorial immune processes are required to determine disease endotypes and response to treatment. OBJECTIVE: To evaluate EO immunomodulation for migration and survival in accordance with inflammatory protein profiles and asthmatic status in CRSwNP. METHODS: Ninety-three patients (47 with asthma) with CRSwNP were included. Each patient was staged clinically according to symptom severity and polyp size. Nasal secretions were collected to establish a cytokine profile. The EOs were purified from blood samples and nasal polyps to delineate specific immunophenotypes by flow cytometry and determine in vitro EO survival in relation to asthmatic status. RESULTS: The CRSwNP in patients with asthma was characterized by eosinophilia and a high level of interleukin (IL)-5 in nasal secretions. Although EOs exhibited activation profiles after mucosal migration, there was relative down-expression of IL-5 receptor-α (IL-5Rα) on nasal EOs in patients with asthma. The EO culture with IL-5 and IL-9 showed an antiapoptotic effect in patients with asthma through IL-5Rα modulation. CONCLUSION:Mucosal eosinophilia seems to be induced by EO nasal trapping through modulation of adhesion receptors. In patients with asthma, EO involvement is enhanced by the antiapoptotic synergistic action of T-helper cell type 2 cytokines on IL-5Rα expression. This study shows for the first time that IL-9 is involved in EO homeostasis in CRSwNP and could explain the low benefit of anti-IL-5 therapy for some patients with asthma and nasal polyposis.
Authors: Youn Ho Shin; Hwan Soo Kim; Eu Kyoung Lee; Young Joo Kim; Hyun-Seung Lee; Pil-Sang Jang; Young-Hoon Kim; Yoon Hong Chun; Jong-Seo Yoon; Hyun Hee Kim; Young-Yull Koh; Jin Tack Kim Journal: Ann Saudi Med Date: 2015 Jul-Aug Impact factor: 1.526