Administration of IL-33 induces airway hyperresponsiveness and goblet cell hyperplasia in the lungs in the absence of adaptive immune system
Administration of IL-33 induces airway hyperresponsiveness and goblet cell hyperplasia in the lungs in the absence of adaptive immune system
复制标题
DOI：
10.1093/intimm/dxn037
复制
发表时间：
2008-06-01
影响因子：
4.4
通讯作者：
Nakanishi, Kenji
中科院分区：
文献类型：
--
作者：
Kondo, Yuichi;Yoshimoto, Tomohiro;Nakanishi, Kenji
全身给予IL-18通过引起NKT细胞表达CD 40配体并产生IL-4来诱导多克隆IgE反应。IL-33的施用也诱导IgE应答，尽管IgE应答的潜在机制尚不清楚。在此，我们比较了IL-18和IL-33对骨髓来源的肥大细胞和嗜碱性粒细胞以及非极化和T（h）2极化的CD 4（+）T细胞的作用。嗜碱性粒细胞，包括IL-18 R α（+）细胞（14.2%）和IL-33 R α（+）细胞（34.6%）和肥大细胞，包括IL-18 R α（+）细胞（2.0%）和IL-33 R α（+）细胞（95.6%），产生IL-4、IL-6、IL-13、粒细胞巨噬细胞集落刺激因子（GM-CSF）和趋化因子（RANTES、MIP-1 α、MIP-1 β和MCP-1），在IL-3存在下用IL-18和/或IL-33刺激后。只有嗜碱性粒细胞强烈产生IL-4。此外，与肥大细胞相比，嗜碱性粒细胞响应于IL-33产生更大量的上述细胞因子和趋化因子。嗜碱性粒细胞IL-33 R β-mRNA表达水平高于肥大细胞。IL-33的作用依赖于ST 2结合，其信号在体外通过MyD 88转导。我们还发现，IL-2加IL-18或IL-33单独刺激非极化或T（h）2极化的CD 4（+）T细胞分别产生IL-4和IL-13或IL-5和IL-13。最后，我们表明，IL-33给药到小鼠ST 2/MyD 88依赖性诱导气道高反应性（AHR）和杯状细胞增生诱导IL-4，IL-5和IL-13在肺中。此外，对缺乏T和B细胞的RAG-2（-/-）小鼠进行相同的处理，更显著地诱导AHR，肺中具有显著的杯状细胞增生和嗜酸性粒细胞浸润。因此，IL-33诱导哮喘样症状完全独立于获得性免疫系统。
Systemic administration of IL-18 induces polyclonal IgE responses by causing NKT cells to express CD40 ligand and to produce IL-4. Administration of IL-33 also induces IgE response, although the mechanism underlying IgE response is unclear. Here, we compared the effects of IL-18 and IL-33 on bone marrow-derived mast cells and basophils as well as non-polarized and T(h)2-polarized CD4(+) T cells in vitro. Basophils, comprising IL-18R alpha(+) cells (14.2%) and IL-33R alpha(+) cells (34.6%), and mast cells, comprising IL-18R alpha(+) cells (2.0%) and IL-33R alpha(+) cells (95.6%), produce IL-4, IL-6, IL-13, granulocyte macrophage colony-stimulating factor (GM-CSF) and chemokines (RANTES, MIP-1 alpha, MIP-1 beta and MCP-1), upon stimulation with IL-18 and/or IL-33 in the presence of IL-3. Only basophils strongly produce IL-4. Furthermore, compared with mast cells, basophils produce larger amounts of the above cytokines and chemokines in response to IL-33. Level of IL-33R beta-mRNA expression in basophils is higher than that in mast cells. Effect of IL-33 is dependent on ST2 binding, and its signal is transduced via MyD88 in vitro. We also found that IL-2 plus IL-18 or IL-33 alone stimulates non-polarized or T(h)2-polarized CD4(+) T cells to produce IL-4 and IL-13 or IL-5 and IL-13, respectively. We finally showed that administration of IL-33 into mice ST2/MyD88 dependently induces airway hyperresponsiveness (AHR) and goblet cell hyperplasia by induction of IL-4, IL-5 and IL-13 in the lungs. Furthermore, same treatment of RAG-2(-/-) mice, lacking T and B cells, more strikingly induced AHR with marked goblet cell hyperplasia and eosinophilic infiltration in the lungs. Thus, IL-33 induces asthma-like symptom entirely independent of acquired immune system.