IL-5-induced hypereosinophilia suppresses the antigen-induced immune response via a TGF-β-dependent mechanism

Kazuyuki Nakagome, Makoto Dohi, Katsuhide Okunishi, Ryoichi Tanaka, Taku Kouro, Mitsunobu Kano, Kohei Miyazono, Jun Ichi Miyazaki, Kiyoshi Takatsu, Kazuhiko Yamamoto

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Abstract

Although eosinophils play an essential role in allergic inflammation, their role has recently been under controversy. Epidemic studies suggest that hypereosinophilia induced by parasite infection could suppress subsequent Ag sensitization, although the mechanism has not been fully clarified. In this study, we investigated whether eosinophils could suppress the Ag-specific immune response in the airway. BALB/c mice were sensitized and airway challenged with OVA. Systemic hypereosinophilia was induced by delivery of an IL-5-producing plasmid. IL-5 gene delivery suppressed the Ag-specific proliferation and cytokine production of CD4+ T cells in the spleen. IL-5 gene delivery before OVA sensitization significantly suppressed airway eosinophilia and hyperresponsiveness provoked by subsequent OVA airway challenge, while delivery during the OVA challenge did not suppress them. This IL-5-induced immune suppression was abolished in eosinophil-ablated mice, suggesting an essential role of eosinophils. IL-5 treatment increased the production of TGF-β1 in the spleen, and we demonstrated that the main cellular source of TGF-β1 production was eosinophils, using eosinophil-ablated mice and depletion study. TGF-β1, but not IL-5 itself, suppressed the Ag-specific immune response of CD4+ T cells in vitro. Furthermore, IL-5 treatment enhanced phosphorylation of Smad2 in CD4+ T cells. Finally, a TGF-β type I receptor kinase inhibitor restored this IL-5-induced immune suppression both in vitro and in vivo. These results suggest that IL-5-induced hypereosinophilia could suppress sensitization to Ag via a TGF-β-dependent mechanism, thus suppressed allergic airway inflammation. Therefore, hypereosinophilia could reveal an immunosuppressive effect in the early stage of Ag-induced immune response.

Original languageEnglish
Pages (from-to)284-294
Number of pages11
JournalJournal of Immunology
Volume179
Issue number1
Publication statusPublished - Jul 1 2007
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

Cite this

Nakagome, K., Dohi, M., Okunishi, K., Tanaka, R., Kouro, T., Kano, M., Miyazono, K., Miyazaki, J. I., Takatsu, K., & Yamamoto, K. (2007). IL-5-induced hypereosinophilia suppresses the antigen-induced immune response via a TGF-β-dependent mechanism. Journal of Immunology, 179(1), 284-294.