1. Contribution of IL-33 to induction and augmentation of experimental allergic conjunctivitis.
- Author
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Matsuba-Kitamura, Saori, Yoshimoto, Tomohiro, Yasuda, Koubun, Futatsugi-Yumikura, Shizue, Taki, Yuuko, Muto, Taichiro, Ikeda, Tomohiro, Mimura, Osamu, and Nakanishi, Kenji
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CYTOKINES ,CONJUNCTIVITIS ,TH2 cells ,BASOPHILS ,INFLAMMATION ,MAST cells - Abstract
IL-33, a member of the IL-1 family of cytokines, is the ligand for ST2 (IL-33Rα chain). IL-33 has the capacity to induce Th2 cytokine production from Th2 cells, mast cells and basophils, indicating that IL-33 has the potential to induce Th2 cytokine-mediated allergic inflammation of the eye. Thus, we tested the pathological role of IL-33 in allergic conjunctivitis (AC). As reported elsewhere, animals immunized with ragweed pollen (RW)/alum and boosted with RW/PBS developed AC promptly (within 15 min) and conjunctival eosinophilic inflammation after a delay (within 24 h) in response to eye drop challenge with RW. Furthermore, RW-immunized mice, when topically challenged with both RW and IL-33, developed more striking eosinophilia in their conjunctiva without exacerbation of the clinical AC score. This in vivo IL-33 treatment significantly increased the capacity of T cells in the cervical lymph nodes of RW-immunized mice to produce IL-4, IL-5 and IL-13 upon challenge with anti-CD3 and anti-CD28 antibodies in vitro. Furthermore, the infiltrating cells were largely eosinophils and a small proportion of CD4+ T cells, both of which express ST2. We also found that even splenic eosinophils express ST2 and show increased expression in response to IL-5, granulocyte–macrophage colony-stimulating factor (GM-CSF) or IL-33. Eosinophils, stimulated with IL-5 and/or GM-CSF, are responsive to IL-33, which induces production of IL-4 and chemokines. Finally, we showed that conjunctival tissues constitutively express biologically active IL-33, suggesting that IL-33 might play a crucial role in the induction and augmentation of AC. [ABSTRACT FROM PUBLISHER]
- Published
- 2010
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