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Synthesized OVA323-339MAP octamers mitigate OVA-induced airway inflammation by regulating Foxp3 T regulatory cells.

Su W, Zhong W, Zhang Y, Xia Z - BMC Immunol. (2012)

Bottom Line: These results were further correlated with the decreased OVA specific immunoglobulin E (sIgE) level and the infiltration of inflammatory cells such as eosinophils and lymphocytes in BALF.However, OVA323-339 peptide monomers did not show any of the mentioned effects in the same animal model.Our study indicates that OVA323-339MAP had significant therapeutic effects on mice allergic airway inflammation by regulating the balance of Th1/Th2 response through Treg cells in vivo.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pediatrics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

ABSTRACT

Background: Antigen-specific immunotherapy (SIT) has been widely practiced in treating allergic diseases such as asthma. However, this therapy may induce a series of allergic adverse events during treatment. Peptide immunotherapy (PIT) was explored to overcome these disadvantages. We confirmed that multiple antigen peptides (MAPs) do not cause autoimmune responses, which led to the presumption that MAPs intervention could alleviate allergic airway inflammation without inducing adverse effects.

Results: In this study, synthesized OVA323-339MAP octamers were subcutaneously injected into ovalbumin (OVA)-sensitized and -challenged Balb/c mice to observe its effect on allergic airway inflammation, Th2 immune response, and immune regulating function. It was confirmed that OVA sensitization and challenge led to significant peritracheal inflammatory, cell infiltration, and intensive Th2 response. Treatment of OVA323-339MAP octomers in the airway inflammation mice model increased CD4+CD25+Foxp3+ T regulatory (Treg) cells and their regulatory function in peripheral blood, mediastinal draining lymph nodes, and the spleen. Furthermore, OVA323-339MAP increased IL-10 levels in bronchial alveolar lavage fluid (BALF); up-regulated the expression of IL-10, membrane-bound TGF-β1, as well as Foxp3 in lung tissues; and up-regulated programmed death-1 (PD-1) and cytotoxic T lymphocyte associated antigen 4 (CTLA-4) on the surface of Treg cells. These results were further correlated with the decreased OVA specific immunoglobulin E (sIgE) level and the infiltration of inflammatory cells such as eosinophils and lymphocytes in BALF. However, OVA323-339 peptide monomers did not show any of the mentioned effects in the same animal model.

Conclusions: Our study indicates that OVA323-339MAP had significant therapeutic effects on mice allergic airway inflammation by regulating the balance of Th1/Th2 response through Treg cells in vivo.

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Related in: MedlinePlus

Impact of OVA323-339and OVA323-339MAP intervention on airway inflammation in mice. After OVA sensitization and challenge, typical airway inflammation was observed in Balb/c mice. The airway inflammation was not significantly alleviated by subcutaneous injection of 200 μg of OVA323-339 peptide monomers. However, OVA323-339MAP, containing the equivalent weight of peptides, significantly reduced peritracheal inflammatory cells infiltration and this effect was dose-dependent. Data represent one of three independent experiments.
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Figure 1: Impact of OVA323-339and OVA323-339MAP intervention on airway inflammation in mice. After OVA sensitization and challenge, typical airway inflammation was observed in Balb/c mice. The airway inflammation was not significantly alleviated by subcutaneous injection of 200 μg of OVA323-339 peptide monomers. However, OVA323-339MAP, containing the equivalent weight of peptides, significantly reduced peritracheal inflammatory cells infiltration and this effect was dose-dependent. Data represent one of three independent experiments.

Mentions: Recently, MAPs have been shown to alleviate the severity and block the progress of EAE [16]. This finding emphasizes the potential of MAPs intervention as an effective immunotherapy to treat antigen-specific allergic diseases. Thus, to examine the impact of MAPs on allergic lung disease, we sensitized Balb/c mice with OVA emulsified in Al(OH)3 and induced airway inflammation by intranasal administration of the antigen. As illustrated in Figures 1 and 2 A, OVA priming and activation led to a high inflammation score associated with marked peribronchial leukocyte infiltration, edema, and epithelial damage. Systemic administration of regular OVA323-339 peptide before local antigen activation did not alter the severity of the airway inflammation and tissue injury, whereas treatment with OVA323-339MAP substantially reduced the inflammatory response in a dose-dependent manner. In addition to the histological evaluation, we assessed airway inflammation by examining total cell counts and eosinophil, neutrophil, lymphocytes and macrophages counts in bronchial alveolar lavage fluid (BALF) of these mice. Compared to the normal control group, OVA sensitization and challenge induced a significant increase of total cells, eosinophils, neutrophils, lymphocytes and macrophages counts, OVA323-339 peptide monomers intervention mildly reduced the total cell count and EOS number. However, a significant decrease in total cell as well as EOS and LYM infiltrates was observed in OVA323-339MAP treated mice (Table 1).


Synthesized OVA323-339MAP octamers mitigate OVA-induced airway inflammation by regulating Foxp3 T regulatory cells.

Su W, Zhong W, Zhang Y, Xia Z - BMC Immunol. (2012)

Impact of OVA323-339and OVA323-339MAP intervention on airway inflammation in mice. After OVA sensitization and challenge, typical airway inflammation was observed in Balb/c mice. The airway inflammation was not significantly alleviated by subcutaneous injection of 200 μg of OVA323-339 peptide monomers. However, OVA323-339MAP, containing the equivalent weight of peptides, significantly reduced peritracheal inflammatory cells infiltration and this effect was dose-dependent. Data represent one of three independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472185&req=5

Figure 1: Impact of OVA323-339and OVA323-339MAP intervention on airway inflammation in mice. After OVA sensitization and challenge, typical airway inflammation was observed in Balb/c mice. The airway inflammation was not significantly alleviated by subcutaneous injection of 200 μg of OVA323-339 peptide monomers. However, OVA323-339MAP, containing the equivalent weight of peptides, significantly reduced peritracheal inflammatory cells infiltration and this effect was dose-dependent. Data represent one of three independent experiments.
Mentions: Recently, MAPs have been shown to alleviate the severity and block the progress of EAE [16]. This finding emphasizes the potential of MAPs intervention as an effective immunotherapy to treat antigen-specific allergic diseases. Thus, to examine the impact of MAPs on allergic lung disease, we sensitized Balb/c mice with OVA emulsified in Al(OH)3 and induced airway inflammation by intranasal administration of the antigen. As illustrated in Figures 1 and 2 A, OVA priming and activation led to a high inflammation score associated with marked peribronchial leukocyte infiltration, edema, and epithelial damage. Systemic administration of regular OVA323-339 peptide before local antigen activation did not alter the severity of the airway inflammation and tissue injury, whereas treatment with OVA323-339MAP substantially reduced the inflammatory response in a dose-dependent manner. In addition to the histological evaluation, we assessed airway inflammation by examining total cell counts and eosinophil, neutrophil, lymphocytes and macrophages counts in bronchial alveolar lavage fluid (BALF) of these mice. Compared to the normal control group, OVA sensitization and challenge induced a significant increase of total cells, eosinophils, neutrophils, lymphocytes and macrophages counts, OVA323-339 peptide monomers intervention mildly reduced the total cell count and EOS number. However, a significant decrease in total cell as well as EOS and LYM infiltrates was observed in OVA323-339MAP treated mice (Table 1).

Bottom Line: These results were further correlated with the decreased OVA specific immunoglobulin E (sIgE) level and the infiltration of inflammatory cells such as eosinophils and lymphocytes in BALF.However, OVA323-339 peptide monomers did not show any of the mentioned effects in the same animal model.Our study indicates that OVA323-339MAP had significant therapeutic effects on mice allergic airway inflammation by regulating the balance of Th1/Th2 response through Treg cells in vivo.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pediatrics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

ABSTRACT

Background: Antigen-specific immunotherapy (SIT) has been widely practiced in treating allergic diseases such as asthma. However, this therapy may induce a series of allergic adverse events during treatment. Peptide immunotherapy (PIT) was explored to overcome these disadvantages. We confirmed that multiple antigen peptides (MAPs) do not cause autoimmune responses, which led to the presumption that MAPs intervention could alleviate allergic airway inflammation without inducing adverse effects.

Results: In this study, synthesized OVA323-339MAP octamers were subcutaneously injected into ovalbumin (OVA)-sensitized and -challenged Balb/c mice to observe its effect on allergic airway inflammation, Th2 immune response, and immune regulating function. It was confirmed that OVA sensitization and challenge led to significant peritracheal inflammatory, cell infiltration, and intensive Th2 response. Treatment of OVA323-339MAP octomers in the airway inflammation mice model increased CD4+CD25+Foxp3+ T regulatory (Treg) cells and their regulatory function in peripheral blood, mediastinal draining lymph nodes, and the spleen. Furthermore, OVA323-339MAP increased IL-10 levels in bronchial alveolar lavage fluid (BALF); up-regulated the expression of IL-10, membrane-bound TGF-β1, as well as Foxp3 in lung tissues; and up-regulated programmed death-1 (PD-1) and cytotoxic T lymphocyte associated antigen 4 (CTLA-4) on the surface of Treg cells. These results were further correlated with the decreased OVA specific immunoglobulin E (sIgE) level and the infiltration of inflammatory cells such as eosinophils and lymphocytes in BALF. However, OVA323-339 peptide monomers did not show any of the mentioned effects in the same animal model.

Conclusions: Our study indicates that OVA323-339MAP had significant therapeutic effects on mice allergic airway inflammation by regulating the balance of Th1/Th2 response through Treg cells in vivo.

Show MeSH
Related in: MedlinePlus