Humphreys Neil E, Xu Damo, Hepworth Matthew R, Liew Foo Y, Grencis Richard K
Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, United Kingdom.
J Immunol. 2008 Feb 15;180(4):2443-9. doi: 10.4049/jimmunol.180.4.2443.
IL-33 (IL-1F11) binds ST2 (IL-1R4), both of which are associated with optimal CD4(+) Th2 polarization. Exogenous IL-33 drives induction of Th2-associated cytokines and associated pathological changes within the gut mucosa. Th2 polarization is also a prerequisite to expulsion of the intestinal-dwelling nematode Trichuris muris. In this study, we demonstrate that IL-33 mRNA is expressed early during parasite infection and susceptible mice can be induced to expel the parasite by a regime of exogenous IL-33 administration. IL-33 prevents an inappropriate parasite-specific Th1-polarized response and induces IL-4, IL-9, and IL-13. This redirection requires the presence of T cells and must occur at the initiation of the response to the pathogen. Interestingly, exogenous IL-33 also induced thymic stromal lymphopoietin mRNA within the infected caecum, an epithelial cell-restricted cytokine essential for the generation of Th2-driven parasite immunity. IL-33 also acts independently of T cells, altering intestinal pathology in chronically infected SCID mice, leading to an increased crypt length and intestinal epithelial cell proliferation, but reducing goblet cell hyperplasia. Thus, the ability of IL-33 to induce Th2 responses has functional relevance in the context of intestinal helminth infection, particularly during the initiation of the response.
白细胞介素-33（IL-33，即IL-1F11）与ST2（IL-1R4）结合，二者均与最佳的CD4(+)辅助性T细胞2型（Th2）极化相关。外源性IL-33可驱动肠道黏膜内Th2相关细胞因子的诱导及相关病理变化。Th2极化也是驱除肠道寄生线虫毛首鞭形线虫的前提条件。在本研究中，我们证明IL-33信使核糖核酸（mRNA）在寄生虫感染早期表达，且通过外源性IL-33给药方案可诱导易感小鼠驱除寄生虫。IL-33可防止不适当的寄生虫特异性Th1极化反应，并诱导白细胞介素-4（IL-4）、白细胞介素-9（IL-9）和白细胞介素-13（IL-13）。这种重定向需要T细胞的存在，且必须在对病原体的反应开始时发生。有趣的是，外源性IL-33还可在受感染的盲肠内诱导胸腺基质淋巴细胞生成素mRNA，胸腺基质淋巴细胞生成素是一种上皮细胞限制性细胞因子，对Th2驱动的寄生虫免疫的产生至关重要。IL-33也可独立于T细胞发挥作用，改变慢性感染的重症联合免疫缺陷（SCID）小鼠的肠道病理，导致隐窝长度增加和肠上皮细胞增殖，但减少杯状细胞增生。因此，在肠道蠕虫感染的背景下，尤其是在反应开始时，IL-33诱导Th2反应的能力具有功能相关性。
