Interleukin-25 and mucosal T cells in noneosinophilic and eosinophilic chronic rhinosinusitis

Interleukin-25 and mucosal T cells in noneosinophilic and eosinophilic chronic rhinosinusitis
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DOI:
10.1016/j.anai.2015.01.013
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发表时间:
2015-04-01
影响因子:
5.9
通讯作者:
Nakayama, Toshinori
Nakayama, Toshinori
中科院分区:
医学2区
文献类型:
--
作者:
Iinuma, Tomohisa;Okamoto, Yoshitaka;Nakayama, Toshinori

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背景:慢性鼻窦炎伴鼻息肉(CRSwNP)是一种异质性疾病,其发病机制尚不明确。目的:探讨白细胞介素(IL)-25对非嗜酸性粒细胞性CRSwNP(NECRS)和嗜酸性粒细胞性CRSwNP(ECRS)患者组织记忆性CD 4(+)T细胞特性的影响。从CRSwNP患者的NP中分离NP单核细胞和CD 4(+)T细胞。采用酶联免疫吸附试验、流式细胞术和实时荧光定量聚合酶链反应(real-time polymerase chain reaction,RT-PCR)检测细胞因子表达和CD 4(+)T细胞亚群。ECRS患者外周血CD 4 + T细胞表达IL-5和IL-9 mRNA水平显著升高。ECRS和NECRS中大多数浸润性CD 4(+)T细胞表达CD 45 RO;然而,无论特应性状态如何,在ECRS患者的CD 4(+)T细胞中检测到高IL-17 RB水平。组织CD 4(+)T细胞表达的IL-17 RB mRNA水平与NP中嗜酸性粒细胞的数量显著相关。在T细胞受体刺激下,用IL-25刺激,ECRS患者的NP单核细胞产生IL-5和IL-9,但在NECRS患者的NP单核细胞中没有发现。白细胞介素-25和组织辅助性T细胞2型和9型亚群表达增加的白细胞介素-25,17 RB水平可能有助于NPs中嗜酸性粒细胞的浸润,并可能产生NECRS和ECRS之间的病理差异。(C)2015年美国过敏,哮喘和免疫学学院。爱思唯尔公司出版All rights reserved.
Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease of uncertain pathogenesis. Memory T cells acquire additional functions during the secondary response and play important roles in chronic inflammation.Objective: To investigate characteristics of tissue memory CD4(+) T cells obtained from patients with non-eosinophilic CRSwNP (NECRS) and eosinophilic CRSwNP (ECRS) by focusing on the influence of interleukin (IL)-25.Methods: Pro-allergic cytokines in tissue homogenates were measured using enzyme-linked immunosorbent assays. NP mononuclear cells and CD4(+) T cells were isolated from NPs from patients with CRSwNP. Cytokine expression and CD4(+) T-cell subpopulations were analyzed using enzyme-linked immunosorbent assay, flow cytometry, and real-time polymerase chain reaction.Results: The IL-25 level in NPs increased in patients with ECRS. IL-5 and IL-9 mRNA levels expressed by tissue CD4(+) T cells were significantly elevated in patients with ECRS. Most infiltrating CD4(+) T cells in ECRS and NECRS expressed CD45RO; however, regardless of the atopic status, high IL-17RB levels were detected in CD4(+) T cells from patients with ECRS. IL-17RB mRNA levels expressed by tissue CD4(+) T cells significantly correlated with the number of eosinophils in NPs. Elevation of IL-5 and IL-9 production was found in NP mononuclear cells from patients with ECRS, but not in those from patients with NECRS, by stimulation with IL-25 under T-cell receptor stimulation.Conclusion: Interleukin-25 and a subpopulation of tissue T-helper type 2 and 9 cells that express increased IL-17RB levels could contribute to infiltration of eosinophils in NPs and could have produced the pathologic difference between NECRS and ECRS. (C) 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.