1. Contribution of IL-33 to induction and augmentation of experimental allergic conjunctivitis.
- Author
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Matsuba-Kitamura S, Yoshimoto T, Yasuda K, Futatsugi-Yumikura S, Taki Y, Muto T, Ikeda T, Mimura O, and Nakanishi K
- Subjects
- Alum Compounds administration & dosage, Ambrosia, Animals, Antigens, Plant administration & dosage, Antigens, Plant immunology, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes metabolism, CD4-Positive T-Lymphocytes pathology, Conjunctiva immunology, Conjunctiva metabolism, Conjunctiva pathology, Conjunctivitis, Allergic physiopathology, Cytokines biosynthesis, Cytokines genetics, Cytokines metabolism, Eosinophilia, Humans, Immunization, Secondary, Interleukin-1 Receptor-Like 1 Protein, Interleukin-33, Lymphocyte Activation drug effects, Mice, Mice, Inbred BALB C, Models, Animal, Pollen immunology, Receptors, Interleukin genetics, CD4-Positive T-Lymphocytes drug effects, Conjunctiva drug effects, Conjunctivitis, Allergic immunology, Interleukins administration & dosage, Receptors, Interleukin metabolism
- Abstract
IL-33, a member of the IL-1 family of cytokines, is the ligand for ST2 (IL-33Ralpha chain). IL-33 has the capacity to induce T(h)2 cytokine production from T(h)2 cells, mast cells and basophils, indicating that IL-33 has the potential to induce T(h)2 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.
- Published
- 2010
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