Abstract

BackgroundAntigen-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.ResultsIn 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.ConclusionsOur 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.

Highlights

  • Antigen-specific immunotherapy (SIT) has been widely practiced in treating allergic diseases such as asthma

  • OVA323-339MAP intervention attenuates OVA-induced airway inflammation Recently, multiple antigen peptide (MAP) 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

  • 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

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Summary

Introduction

Antigen-specific immunotherapy (SIT) has been widely practiced in treating allergic diseases such as asthma. This therapy may induce a series of allergic adverse events during treatment. Janssen et al [15] found that OVA323-339 peptides containing major T cell epitopes of ovalbumin (OVA) proteins do not mitigate the effects of airway inflammation, but aggravate disease in OVA-induced asthmatic mice. Wegman et al.[16] found that PLP139-151 peptide (proteolipid protein) monomers had no effect in improving disease, while synthesized PLP139-151 multiple antigen peptide (MAP) octamers successfully inhibited the occurrence of EAE induced by encephalitis pathogenic protein, demonstrating that peptide monomers processing can alter their immunological characteristics

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