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转移因子肽(Imuno TF)可调节变应性哮喘中的肺部炎症和气道重塑。

Transfer factors peptides (Imuno TF) modulate the lung inflammation and airway remodeling in allergic asthma.

机构信息

Medical School, Group of Phytocomplexes and Cell Signaling, Anhembi Morumbi University, São José dos Campos, São Paulo, Brazil.

Postgraduate Program in Biomedical Engineering, Anhembi Morumbi University, Sao Jose dos Campos, São Paulo, Brazil.

出版信息

Front Immunol. 2023 Jan 4;13:1030252. doi: 10.3389/fimmu.2022.1030252. eCollection 2022.

Abstract

BACKGROUND

Allergic asthma is a chronic lung disease in which the lung inflammation and airway remodeling are orchestrated by both the inflammatory and the immune cells that creates a lung millieu that favors the perpetuation of clinical symptoms. The cell signaling in asthma involves the mast cells activation during initial contact with the allergen and, principally, the participation of eosinophils as well as Th2 cells which determine increased levels of IgE, exaggerated secretion of mucus and collagen, and bronchial hyperreactivity. Moreover, allergic asthma presents lower level of cytokines associated to the both Th1 and Treg cells response, and it implies in deficiency of anti-inflammatory response to counterregulate the exaggerated inflammation against allergen. Therefore, the equilibrium between cytokines as well as transcription factors associated to Th2, Th1, and Treg cells is compromised in allergic asthma. Imuno TF is a food supplement with ability to interfere in immune system pathways. It has been previously demonstrated that Imuno TF upregulated Th1 cell response whilst downregulated Th2 cell response in human lymphocytes.

OBJECTIVE

For this reason, we hypothesized that the Imuno TF effect could be restore the balance between Th1/Th2 CD4 T cells response in murine allergic asthma.

METHODS

Initially, animals were sensitized with OVA i.p. and challenged with OVA i.n. on days 14, 15 and 16. Treatment with Imuno TF once a day was performed orogastric from day 17 to day 20. Mice were euthanized on day 21.

RESULTS

The Imuno TF reduced eosinophilia, mucus production, and airway remodeling (collagen deposition) in asthma mice. Imuno TF influenced cellular signaling associated to allergic asthma once downregulated STAT6 expression as well as decreased IL-4, IL-5, and IL-13 in lung and serum. In addition, Imuno TF restored T-bet and Foxp3 expression as well as increased IL-12, IFN-ɣ, and IL-10.

CONCLUSION

Ultimately, Imuno TF mitigated the allergic asthma due to the restoration of balance between the responses of Th1/Th2 as well as Treg cells, and their respective transcription factors the T-bet/STAT6 and Foxp3.

摘要

背景

过敏性哮喘是一种慢性肺部疾病,其中肺部炎症和气道重塑是由炎症细胞和免疫细胞共同协调的,形成了一个有利于临床症状持续存在的肺部环境。哮喘中的细胞信号转导涉及到肥大细胞在初次接触过敏原时的激活,主要涉及到嗜酸性粒细胞以及 Th2 细胞的参与,这些细胞会导致 IgE 水平升高、黏液和胶原过度分泌以及支气管高反应性。此外,过敏性哮喘表现出较低水平的与 Th1 和 Treg 细胞反应相关的细胞因子,这意味着对抗过敏原的炎症反应缺乏抗炎反应的调节。因此,过敏性哮喘中与 Th2、Th1 和 Treg 细胞相关的细胞因子和转录因子之间的平衡被打破。Imuno TF 是一种具有干扰免疫系统途径能力的膳食补充剂。先前的研究表明,Imuno TF 上调了人类淋巴细胞中的 Th1 细胞反应,同时下调了 Th2 细胞反应。

目的

因此,我们假设 Imuno TF 的作用可能是恢复过敏性哮喘中 Th1/Th2 CD4 T 细胞反应之间的平衡。

方法

最初,动物通过腹腔注射 OVA 致敏,并在第 14、15 和 16 天通过鼻内注射 OVA 进行攻毒。从第 17 天到第 20 天,每天通过口服给予 Imuno TF 进行治疗。第 21 天处死小鼠。

结果

Imuno TF 减少了哮喘小鼠的嗜酸性粒细胞浸润、黏液产生和气道重塑(胶原沉积)。Imuno TF 影响了与过敏性哮喘相关的细胞信号转导,下调了 STAT6 表达,并降低了肺和血清中的 IL-4、IL-5 和 IL-13。此外,Imuno TF 恢复了 T-bet 和 Foxp3 的表达,并增加了 IL-12、IFN-γ 和 IL-10。

结论

最终,Imuno TF 通过恢复 Th1/Th2 以及 Treg 细胞反应及其相应的转录因子 T-bet/STAT6 和 Foxp3 之间的平衡,减轻了过敏性哮喘。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74c9/9846599/5571f389094c/fimmu-13-1030252-g001.jpg

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