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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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FCM detection of CD4+CD25+Foxp3+Treg cells in peripheral blood, mediastinal draining lymph nodes, and spleen of mice. In vivo OVA challenge could decrease the level of Treg cells in the mice. However, the levels of local and peripheral CD4+CD25+Foxp3+ Treg cells was about 0.5-1.0-fold increase after OVA323-339MAP treatment (gating on CD4+ T cell populations, * compared with the control group, P < 0.05; # compared with the OVA group, P < 0.05). Data represent one of three independent experiments.
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Figure 5: FCM detection of CD4+CD25+Foxp3+Treg cells in peripheral blood, mediastinal draining lymph nodes, and spleen of mice. In vivo OVA challenge could decrease the level of Treg cells in the mice. However, the levels of local and peripheral CD4+CD25+Foxp3+ Treg cells was about 0.5-1.0-fold increase after OVA323-339MAP treatment (gating on CD4+ T cell populations, * compared with the control group, P < 0.05; # compared with the OVA group, P < 0.05). Data represent one of three independent experiments.

Mentions: In light of these findings, we evaluated whether OVA323-339MAP induces peripheral tolerance as a part of a potential mechanism for mitigating OVA-induced airway inflammation. Treg cells regulate the functions of other CD4+CD25- effector cells and play an important role in balancing Th1/Th2 cell differentiation. Therefore, we observed the alteration of Treg cells. CD4+CD25+Foxp3+ Treg cells in peripheral blood, mediastinal draining lymph nodes, and spleen were measured by FCM. In vivo OVA challenge decreased the level of Treg cells in the mice. However, OVA323-339MAP increased the population of local and peripheral CD4+CD25+Foxp3+ Treg cells approximately 0.5-1.0 fold (Figure 5). In addition, we further detected the Foxp3 transcription expression in the lung to observed Treg cells in inflamed local tissue. The result showed that Foxp3 expression in the lung was augmented by MAPs intervention (Figure 3 J).


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)

FCM detection of CD4+CD25+Foxp3+Treg cells in peripheral blood, mediastinal draining lymph nodes, and spleen of mice. In vivo OVA challenge could decrease the level of Treg cells in the mice. However, the levels of local and peripheral CD4+CD25+Foxp3+ Treg cells was about 0.5-1.0-fold increase after OVA323-339MAP treatment (gating on CD4+ T cell populations, * compared with the control group, P < 0.05; # compared with the OVA group, P < 0.05). 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 5: FCM detection of CD4+CD25+Foxp3+Treg cells in peripheral blood, mediastinal draining lymph nodes, and spleen of mice. In vivo OVA challenge could decrease the level of Treg cells in the mice. However, the levels of local and peripheral CD4+CD25+Foxp3+ Treg cells was about 0.5-1.0-fold increase after OVA323-339MAP treatment (gating on CD4+ T cell populations, * compared with the control group, P < 0.05; # compared with the OVA group, P < 0.05). Data represent one of three independent experiments.
Mentions: In light of these findings, we evaluated whether OVA323-339MAP induces peripheral tolerance as a part of a potential mechanism for mitigating OVA-induced airway inflammation. Treg cells regulate the functions of other CD4+CD25- effector cells and play an important role in balancing Th1/Th2 cell differentiation. Therefore, we observed the alteration of Treg cells. CD4+CD25+Foxp3+ Treg cells in peripheral blood, mediastinal draining lymph nodes, and spleen were measured by FCM. In vivo OVA challenge decreased the level of Treg cells in the mice. However, OVA323-339MAP increased the population of local and peripheral CD4+CD25+Foxp3+ Treg cells approximately 0.5-1.0 fold (Figure 5). In addition, we further detected the Foxp3 transcription expression in the lung to observed Treg cells in inflamed local tissue. The result showed that Foxp3 expression in the lung was augmented by MAPs intervention (Figure 3 J).

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