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

21 Citations (Scopus)

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

Fingerprint

Chemokine CCL11
Allergic Conjunctivitis
Immediate Hypersensitivity
Chemokine Receptors
Mast Cells
Immunoglobulin E
Hypersensitivity
Connective Tissue Cells
Cell Degranulation
Conjunctiva
T-Cell Antigen Receptor
Allergens
T-Lymphocytes

Keywords

  • Mast cell

ASJC Scopus subject areas

  • Immunology

Cite this

Miyazaki, D., Nakamura, T., Ohbayashi, M., Kuo, C. H., Komatsu, N., Yakura, K., ... 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

Ablation of type I hypersensitivity in experimental allergic conjunctivitis by eotaxin-1/CCR3 blockade. / Miyazaki, Dai; Nakamura, Takao; Ohbayashi, Masaharu; Kuo, Chuan Hui; Komatsu, Naoki; Yakura, Keiko; Tominaga, Takeshi; Inoue, Yoshitsugu; Higashi, Hidemitsu; Murata, Meguru; Takeda, Shuzo; Fukushima, Atsuki; Liu, Fu-Tong; Rothenberg, Marc E.; Ono, Santa Jeremy.

In: International Immunology, Vol. 21, No. 2, 2009, p. 187-201.

Research output: Contribution to journalArticle

Miyazaki, D, Nakamura, T, Ohbayashi, M, Kuo, CH, Komatsu, N, Yakura, K, Tominaga, T, Inoue, Y, Higashi, H, Murata, M, Takeda, S, Fukushima, A, Liu, F-T, Rothenberg, ME & Ono, SJ 2009, 'Ablation of type I hypersensitivity in experimental allergic conjunctivitis by eotaxin-1/CCR3 blockade', International Immunology, vol. 21, no. 2, pp. 187-201. https://doi.org/10.1093/intimm/dxn137
Miyazaki, Dai ; Nakamura, Takao ; Ohbayashi, Masaharu ; Kuo, Chuan Hui ; Komatsu, Naoki ; Yakura, Keiko ; Tominaga, Takeshi ; Inoue, Yoshitsugu ; Higashi, Hidemitsu ; Murata, Meguru ; Takeda, Shuzo ; Fukushima, Atsuki ; Liu, Fu-Tong ; Rothenberg, Marc E. ; Ono, Santa Jeremy. / Ablation of type I hypersensitivity in experimental allergic conjunctivitis by eotaxin-1/CCR3 blockade. In: International Immunology. 2009 ; Vol. 21, No. 2. pp. 187-201.
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