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Effects of Local Nasal Immunotherapy with FIP-fve Peptide and Denatured Tyrophagus putrescentiae for Storage Mite-Induced Airway Inflammation
Archivum Immunologiae et Therapiae Experimentalis ( IF 3.2 ) Pub Date : 2022-01-31 , DOI: 10.1007/s00005-022-00645-w
Chung-Yang Yen , Ching-Hsiang Yu , Jaw-Ji Tsai , Hsiang-Kuang Tseng , En-Chih Liao

Allergic diseases are affecting public health and have increased over the last decade. Sensitization to mite allergens is a considerable trigger for allergy development. Storage mite-Tyrophagus putrescentiae shows great significance of allergenic potential and clinical relevance. The fungal immunomodulatory peptide FIP-fve has been reported to possess immunomodulatory activity. We aimed to determine whether T. putrescentiae-induced sensitization and airway inflammation in mice could be downregulated by FIP-fve in conjunction with denatured T. putrescentiae (FIP-fve and DN-Tp). Immune responses and physiologic variations in immunoglobulins, leukocyte subpopulations, cytokine productions, pulmonary function, lung pathology, cytokines in CD4+ and Treg cells were evaluated after local nasal immunotherapy (LNIT). After the LNIT with FIP-fve and DN-Tp, levels of specific IgE, IgG1, and IgG2a in the sera and IgA in the bronchoalveolar lavage fluid (BALF) were significantly reduced. Infiltrations of inflammatory leukocytes (eosinophils, neutrophils, and lymphocytes) in the airway decreased significantly. Production of proinflammatory cytokines (IL-5, IL-13, IL-17F and IL-23) and chemokine (IL-8) were significantly reduced, and Th1-cytokine (IL-12) increased in the airway BALF after LNIT. Pulmonary functions of Penh values were significantly decreased after the methacholine challenge, which resulted in a reduction of airway hypersensitivity after LNIT. Bronchus pathology showed a reduction of inflammatory cell infiltration and epithelium damage after LNIT. The IL-4+/CD4+ T cells could be downregulated and the IFN-γ+/CD4+ T cells upregulated. The Treg-related immunity of IL-10 and Foxp3 expressions in CD4+CD25+ cells were both upregulated after LNIT. In conclusion, LNIT with FIP-fve and DN-Tp had an anti-inflammatory effect on mite-induced airway inflammations and possesses potential as an immunomodulatory therapy agent for allergic airway diseases.



中文翻译:

FIP-fve 肽和变性腐食腐食菌局部鼻腔免疫治疗对储存螨引起的气道炎症的影响

过敏性疾病正在影响公共健康,并且在过去十年中有所增加。对螨过敏原敏感是过敏发展的重要诱因。贮藏螨 - Tyrophagus putrescentiae显示出过敏潜力和临床相关性的重要意义。据报道,真菌免疫调节肽 FIP - fve具有免疫调节活性。我们的目的是确定FIP- fve与变性的T. putrescentiae(FIP - fve和 DN-Tp)一起是否可以下调小鼠中T. putrescentiae诱导的致敏和气道炎症在局部鼻腔免疫治疗 (LNIT) 后评估免疫球蛋白、白细胞亚群、细胞因子产生、肺功能、肺病理学、CD4 +和 Treg 细胞中的细胞因子的免疫反应和生理变化。在具有 FIP-fve 和 DN-Tp 的LNIT之后血清中特异性 IgE、IgG1 和 IgG2a 以及支气管肺泡灌洗液 (BALF) 中的 IgA 水平显着降低。气道中炎性白细胞(嗜酸性粒细胞、中性粒细胞和淋巴细胞)的浸润显着减少。LNIT 后气道 BALF 中促炎细胞因子(IL-5、IL-13、IL-17F 和 IL-23)和趋化因子(IL-8)的产生显着减少,Th1 细胞因子(IL-12)增加。Penh 值的肺功能在乙酰甲胆碱攻击后显着降低,这导致 LNIT 后气道超敏反应降低。支气管病理学显示LNIT后炎症细胞浸润和上皮损伤减少。IL-4 + /CD4 + T 细胞可能被下调,而 IFN-γ +/CD4 + T 细胞上调。在 LNIT 后,CD4 + CD25 +细胞中 IL-10 和 Foxp3 表达的 Treg 相关免疫均上调。总之,含有 FIP-fveDN-Tp 的 LNIT 对螨虫引起的气道炎症具有抗炎作用,并具有作为过敏性气道疾病的免疫调节治疗剂的潜力。

更新日期:2022-01-31
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