Ablation of type I hypersensitivity in experimental allergic conjunctivitis by eotaxin-1/CCR3 blockade

Dai Miyazaki, Takao Nakamura, Masaharu Ohbayashi, Chuan Hui Kuo, Naoki Komatsu, Keiko Yakura, Takeshi Tominaga, Yoshitsugu Inoue, Hidemitsu Higashi, Meguru Murata, Shuzo Takeda, Atsuki Fukushima, Fu-Tong Liu, Marc E. Rothenberg, Santa Jeremy Ono

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The immune response is regulated, in part, by effector cells whose activation requires multiple signals. For example, T cells require signals emanating from the T cell antigen receptor and co-stimulatory molecules for full activation. Here, we present evidence indicating that IgE-mediated hypersensitivity reactions in vivo also require cognate signals to activate mast cells. Immediate hypersensitivity reactions in the conjunctiva are ablated in mice deficient in eotaxin-1, despite normal numbers of tissue mast cells and levels of IgE. To further define the co-stimulatory signals mediated by chemokine receptor 3 (CCR3), an eotaxin-1 receptor, effects of CCR3 blockade were tested with an allergic conjunctivitis model and in ex vivo isolated connective tissue-type mast cells. Our results show that CCR3 blockade significantly suppresses allergen-mediated hypersensitivity reactions as well as IgE-mediated mast cell degranulation. We propose that a co-stimulatory axis by CCR3, mainly stimulated by eotaxin-1, is pivotal in mast cell-mediated hypersensitivity reactions.

Original languageEnglish (US)
Pages (from-to)187-201
Number of pages15
JournalInternational Immunology
Volume21
Issue number2
DOIs
StatePublished - 2009

Keywords

  • Mast cell

ASJC Scopus subject areas

  • Immunology

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    Miyazaki, D., Nakamura, T., Ohbayashi, M., Kuo, C. H., Komatsu, N., Yakura, K., Tominaga, T., Inoue, Y., Higashi, H., Murata, M., Takeda, S., Fukushima, A., Liu, F-T., Rothenberg, M. E., & Ono, S. J. (2009). Ablation of type I hypersensitivity in experimental allergic conjunctivitis by eotaxin-1/CCR3 blockade. International Immunology, 21(2), 187-201. https://doi.org/10.1093/intimm/dxn137