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 language | English (US) |
|---|---|
| Pages (from-to) | 187-201 |
| Number of pages | 15 |
| Journal | International Immunology |
| Volume | 21 |
| Issue number | 2 |
| DOIs | |
| State | Published - 2009 |
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Keywords
- Mast cell
ASJC Scopus subject areas
- Immunology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Ablation of type I hypersensitivity in experimental allergic conjunctivitis by eotaxin-1/CCR3 blockade
AU - Miyazaki, Dai
AU - Nakamura, Takao
AU - Ohbayashi, Masaharu
AU - Kuo, Chuan Hui
AU - Komatsu, Naoki
AU - Yakura, Keiko
AU - Tominaga, Takeshi
AU - Inoue, Yoshitsugu
AU - Higashi, Hidemitsu
AU - Murata, Meguru
AU - Takeda, Shuzo
AU - Fukushima, Atsuki
AU - Liu, Fu-Tong
AU - Rothenberg, Marc E.
AU - Ono, Santa Jeremy
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
KW - Mast cell
UR - http://www.scopus.com/inward/record.url?scp=59549090280&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=59549090280&partnerID=8YFLogxK
U2 - 10.1093/intimm/dxn137
DO - 10.1093/intimm/dxn137
M3 - Article
C2 - 19147836
AN - SCOPUS:59549090280
VL - 21
SP - 187
EP - 201
JO - International Immunology
JF - International Immunology
SN - 0953-8178
IS - 2
ER -