Contribution of IL-33 to induction and augmentation of experimental allergic conjunctivitis
Contribution of IL-33 to induction and augmentation of experimental allergic conjunctivitis
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DOI：
10.1093/intimm/dxq035
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发表时间：
2010-06-01
影响因子：
4.4
通讯作者：
Nakanishi, Kenji
中科院分区：
文献类型：
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作者：
Matsuba-Kitamura, Saori;Yoshimoto, Tomohiro;Nakanishi, Kenji
IL-33是细胞因子IL-1家族的成员，是ST 2（IL-33 R α链）的配体。IL-33具有诱导T（h）2细胞、肥大细胞和嗜碱性粒细胞产生T（h）2细胞因子的能力，表明IL-33具有诱导T（h）2烟碱介导的眼部过敏性炎症的潜力。因此，我们测试了IL-33在变应性结膜炎（AC）中的病理作用。如其他地方所报道的，用豚草花粉（RW）/明矾免疫并用RW/PBS加强免疫的动物迅速（15分钟内）出现AC，并在RW滴眼液攻击后延迟（24小时内）出现结膜嗜酸性粒细胞炎症。此外，RW免疫的小鼠，当局部攻击RW和IL-33，在他们的结膜发展更显着的嗜酸性粒细胞增多症，而没有恶化的临床AC评分。这种体内IL-33处理显著增加了RW免疫小鼠的颈淋巴结中T细胞在体外用抗CD 3和抗CD 28抗体攻击时产生IL-4、IL-5和IL-13的能力。此外，浸润细胞主要是嗜酸性粒细胞和一小部分CD 4（+）T细胞，两者都表达ST 2。我们还发现，甚至脾嗜酸性粒细胞表达ST 2，并显示响应IL-5，粒细胞-巨噬细胞集落刺激因子（GM-CSF）或IL-33的表达增加。用IL-5和/或GM-CSF刺激的嗜酸性粒细胞响应于IL-33，其诱导IL-4和趋化因子的产生。最后，我们发现结膜组织组成型表达具有生物活性的IL-33，这表明IL-33可能在AC的诱导和增强中起关键作用。
IL-33, a member of the IL-1 family of cytokines, is the ligand for ST2 (IL-33R alpha 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.