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

BMC Immunology

Zhenwei Xia²  Yanjie Zhang¹  Wenwei Zhong¹  Wen Su¹ 

[1] Department of Pediatrics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China;Department of Pediatrics, Ruijin Hospital, Ruijin 2nd Road 197, Shanghai, 200025, China

关键词: Multiple antigen peptide;    Specific immunotherapy;    Allergic airway inflammation;   

Others  :  1077903
DOI  :  10.1186/1471-2172-13-34

 received in 2012-01-19, accepted in 2012-06-27,  发布年份 2012

【 摘 要 】

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 OVA_323-339MAP 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 OVA_323-339MAP 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, OVA_323-339MAP 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, OVA_323-339 peptide monomers did not show any of the mentioned effects in the same animal model.

Conclusions

Our study indicates that OVA_323-339MAP had significant therapeutic effects on mice allergic airway inflammation by regulating the balance of Th1/Th2 response through Treg cells in vivo.

【 授权许可】

   
2012 Su et al.; licensee BioMed Central Ltd.

【 图 表 】

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