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IL-23 和 IL-17 在变应性鼻炎小鼠模型中的免疫调节作用。

Immunomodulatory effects of IL-23 and IL-17 in a mouse model of allergic rhinitis.

机构信息

Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China.

出版信息

Clin Exp Allergy. 2013 Aug;43(8):956-66. doi: 10.1111/cea.12123.

Abstract

BACKGROUND

Interleukin-23 (IL-23) and IL-17 may be involved in the pathogenesis of allergic rhinitis (AR). However, a differentiation of the role of IL-23 and IL-17 has not been performed yet.

OBJECTIVE

The aim of this study was therefore to investigate the immunomodulatory effects of IL-23 and IL-17, using a mouse model of AR.

METHODS

Anti-IL-23p19 and anti-IL-17 Abs were administrated intranasally during rechallenge in ovalbumin (OVA)-induced AR in BALB/c mice. Immunomodulatory effects were evaluated by measuring nasal rubbing and sneezing occurrences, serum OVA-specific antibodies, Th2 responses (i.e. expression of IL-4, IL-5, IL-13 and IFN-γ genes in nasal mucosa, IL-4(+) CD4(+) T cells percentages in superficial cervical lymph nodes (LNs) and IL-4 production in LNs stimulated with OVA in vitro), and neutrophil, eosinophil and mast cell recruitment into the nasal mucosa.

RESULTS

The effect of IL-17 antagonism was limited to attenuating the Th2 responses and neutrophil and eosinophil infiltration. In contrast, treatment with anti-IL-23p19 Abs markedly reduced nasal rubbing and sneezing events, Th2 responses, serum OVA-specific IgE and IgG1 levels, as well as mucosal neutrophil, eosinophil and mast cell infiltration.

CONCLUSION AND CLINICAL RELEVANCE

IL-17 and IL-23 may play a pathogenic role in an established AR mouse model; with a more pronounced contribution of IL-23 than IL-17.

摘要

背景

白细胞介素-23(IL-23)和白细胞介素-17(IL-17)可能参与了变应性鼻炎(AR)的发病机制。然而,IL-23 和 IL-17 的作用尚未得到区分。

目的

因此,本研究旨在通过 AR 小鼠模型研究 IL-23 和 IL-17 的免疫调节作用。

方法

在卵清蛋白(OVA)诱导的 BALB/c 小鼠 AR 再激发期间,经鼻腔给予抗 IL-23p19 和抗 IL-17Abs。通过测量鼻摩擦和打喷嚏次数、血清 OVA 特异性抗体、Th2 反应(即鼻黏膜中 IL-4、IL-5、IL-13 和 IFN-γ 基因的表达、浅层颈淋巴结(LNs)中 IL-4(+)CD4(+)T 细胞的百分比以及体外用 OVA 刺激 LNs 产生的 IL-4)以及嗜中性粒细胞、嗜酸性粒细胞和肥大细胞向鼻黏膜的募集,来评估免疫调节作用。

结果

IL-17 拮抗作用仅限于减轻 Th2 反应和嗜中性粒细胞和嗜酸性粒细胞浸润。相比之下,用抗 IL-23p19Abs 治疗可显著减少鼻摩擦和打喷嚏次数、Th2 反应、血清 OVA 特异性 IgE 和 IgG1 水平以及黏膜嗜中性粒细胞、嗜酸性粒细胞和肥大细胞浸润。

结论和临床相关性

IL-17 和 IL-23 可能在已建立的 AR 小鼠模型中发挥致病作用;IL-23 的作用比 IL-17 更为显著。

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