Immunotherapy With Recombinant Alt a 1 Suppresses Allergic Asthma and Influences T Follicular Cells and Regulatory B Cells in Mice

BackgroundAlternaria is a major source of asthma-inducing allergens. Allergen-specific immunotherapy improves the progression of allergic asthma. The current treatment is based on crude Alternaria extracts. Alt a 1 is the predominant allergen in Alternaria. However, the treatment efficacy of recombi...

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Autores principales:	Juan Liu, Jia Yin
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Alternaria recombinant Alt a 1 allergen-specific immunotherapy allergic asthma T follicular cells regulatory B cells Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/aa749f5e1e654be8bce49521ffb60f64
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spelling	oai:doaj.org-article:aa749f5e1e654be8bce49521ffb60f642021-11-05T11:55:52ZImmunotherapy With Recombinant Alt a 1 Suppresses Allergic Asthma and Influences T Follicular Cells and Regulatory B Cells in Mice1664-322410.3389/fimmu.2021.747730https://doaj.org/article/aa749f5e1e654be8bce49521ffb60f642021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.747730/fullhttps://doaj.org/toc/1664-3224BackgroundAlternaria is a major source of asthma-inducing allergens. Allergen-specific immunotherapy improves the progression of allergic asthma. The current treatment is based on crude Alternaria extracts. Alt a 1 is the predominant allergen in Alternaria. However, the treatment efficacy of recombinant Alt a 1 (rAlt a 1) in an asthmatic animal model and its influence on Tfh and Breg cells are unknown.ObjectiveTo explore the therapeutic treatment effects of rAlt a 1 on the progress of an asthmatic mouse model and its effect on Tfh and Breg cells.MethodsWe synthesized and purified rAlt a 1. Alternaria-sensitized and challenged mice received subcutaneous immunotherapy (SCIT) with four different rAlt a 1 dosages (5, 50, 100, and 150 µg) or PBS only. Finally, lung and airway inflammation, mouse mast cell protease 1 (MMCP-1), serum immunoglobulin responses, Tfh and Breg cell levels, and the correlation between asthmatic features (inflammation grades and IL-4 and IL-10 levels) and these two cell types were measured after Alternaria rechallenge.ResultsHigh purity and allergenic potency of rAlt a 1 protein were obtained. Following treatment with four different rAlt a 1 dosages, both lung and airway inflammation ameliorated, including lung pathology, serum MMCP-1 levels, inflammatory cell numbers, and cytokine levels in bronchoalveolar lavage fluid (BALF). Additionally, rAlt a 1-SCIT increased the expression of Alternaria-sIgG1, rAlt a 1-sIgG1, rAlt a 1-sIgG2a, and rAlt a 1-sIgG2b in serum. Moreover, the number and percentage of CXCR5+PD-1+Tfh cells were increased in the PC control, while they decreased in the rAlt a 1-SCIT groups. Meanwhile, the absolute numbers and proportions of Breg cells were evaluated after administration of rAlt a 1. A positive correlation was observed between CXCR5+PD-1+Tfh cells and inflammation grades (r = 0.50, p = 0.01), as well as a slightly strong positive relationship with IL-4 (r = 0.55, p = 0.005) and IL-10 (r = 0.58, p = 0.003) levels; Breg cells showed an opposite correlation with the grades of inflammation (r = -0.68, p = 0.0003), along with a negative correlation to IL-4 (r = -0.61, p = 0.001) and IL-10 (r = -0.53, p = 0.008) levels.ConclusionsWe verified that treatment with rAlt a 1 can alleviate asthma progression and further have a regulatory effect on Tfh and Breg cells in an Alternaria-induced asthmatic mouse model.Juan LiuJuan LiuJuan LiuJia YinJia YinJia YinFrontiers Media S.A.articleAlternariarecombinant Alt a 1allergen-specific immunotherapyallergic asthmaT follicular cellsregulatory B cellsImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Alternaria recombinant Alt a 1 allergen-specific immunotherapy allergic asthma T follicular cells regulatory B cells Immunologic diseases. Allergy RC581-607
spellingShingle	Alternaria recombinant Alt a 1 allergen-specific immunotherapy allergic asthma T follicular cells regulatory B cells Immunologic diseases. Allergy RC581-607 Juan Liu Juan Liu Juan Liu Jia Yin Jia Yin Jia Yin Immunotherapy With Recombinant Alt a 1 Suppresses Allergic Asthma and Influences T Follicular Cells and Regulatory B Cells in Mice
description	BackgroundAlternaria is a major source of asthma-inducing allergens. Allergen-specific immunotherapy improves the progression of allergic asthma. The current treatment is based on crude Alternaria extracts. Alt a 1 is the predominant allergen in Alternaria. However, the treatment efficacy of recombinant Alt a 1 (rAlt a 1) in an asthmatic animal model and its influence on Tfh and Breg cells are unknown.ObjectiveTo explore the therapeutic treatment effects of rAlt a 1 on the progress of an asthmatic mouse model and its effect on Tfh and Breg cells.MethodsWe synthesized and purified rAlt a 1. Alternaria-sensitized and challenged mice received subcutaneous immunotherapy (SCIT) with four different rAlt a 1 dosages (5, 50, 100, and 150 µg) or PBS only. Finally, lung and airway inflammation, mouse mast cell protease 1 (MMCP-1), serum immunoglobulin responses, Tfh and Breg cell levels, and the correlation between asthmatic features (inflammation grades and IL-4 and IL-10 levels) and these two cell types were measured after Alternaria rechallenge.ResultsHigh purity and allergenic potency of rAlt a 1 protein were obtained. Following treatment with four different rAlt a 1 dosages, both lung and airway inflammation ameliorated, including lung pathology, serum MMCP-1 levels, inflammatory cell numbers, and cytokine levels in bronchoalveolar lavage fluid (BALF). Additionally, rAlt a 1-SCIT increased the expression of Alternaria-sIgG1, rAlt a 1-sIgG1, rAlt a 1-sIgG2a, and rAlt a 1-sIgG2b in serum. Moreover, the number and percentage of CXCR5+PD-1+Tfh cells were increased in the PC control, while they decreased in the rAlt a 1-SCIT groups. Meanwhile, the absolute numbers and proportions of Breg cells were evaluated after administration of rAlt a 1. A positive correlation was observed between CXCR5+PD-1+Tfh cells and inflammation grades (r = 0.50, p = 0.01), as well as a slightly strong positive relationship with IL-4 (r = 0.55, p = 0.005) and IL-10 (r = 0.58, p = 0.003) levels; Breg cells showed an opposite correlation with the grades of inflammation (r = -0.68, p = 0.0003), along with a negative correlation to IL-4 (r = -0.61, p = 0.001) and IL-10 (r = -0.53, p = 0.008) levels.ConclusionsWe verified that treatment with rAlt a 1 can alleviate asthma progression and further have a regulatory effect on Tfh and Breg cells in an Alternaria-induced asthmatic mouse model.
format	article
author	Juan Liu Juan Liu Juan Liu Jia Yin Jia Yin Jia Yin
author_facet	Juan Liu Juan Liu Juan Liu Jia Yin Jia Yin Jia Yin
author_sort	Juan Liu
title	Immunotherapy With Recombinant Alt a 1 Suppresses Allergic Asthma and Influences T Follicular Cells and Regulatory B Cells in Mice
title_short	Immunotherapy With Recombinant Alt a 1 Suppresses Allergic Asthma and Influences T Follicular Cells and Regulatory B Cells in Mice
title_full	Immunotherapy With Recombinant Alt a 1 Suppresses Allergic Asthma and Influences T Follicular Cells and Regulatory B Cells in Mice
title_fullStr	Immunotherapy With Recombinant Alt a 1 Suppresses Allergic Asthma and Influences T Follicular Cells and Regulatory B Cells in Mice
title_full_unstemmed	Immunotherapy With Recombinant Alt a 1 Suppresses Allergic Asthma and Influences T Follicular Cells and Regulatory B Cells in Mice
title_sort	immunotherapy with recombinant alt a 1 suppresses allergic asthma and influences t follicular cells and regulatory b cells in mice
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/aa749f5e1e654be8bce49521ffb60f64
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Immunotherapy With Recombinant Alt a 1 Suppresses Allergic Asthma and Influences T Follicular Cells and Regulatory B Cells in Mice

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