固有免疫细胞Nuocytes介导Th2免疫应答
2010/12/07
固有免疫应答是机体防御病原体入侵的第一道防线，同时也促成了适应性免疫应答的形成。发生蠕虫等寄生虫感染时机体的保护性免疫应答是Th2免疫应答，而过度的Th2免疫应答也是变应性哮喘的发病机制。IL-4、IL-5、IL-13等Th2类细胞因子的产生在Th2免疫应答中起到重要作用。这些细胞因子主要来源于适应性免疫细胞-T细胞，而哪些固有免疫细胞可以产生这些细胞因子目前仍不清楚。
为此，Daniel R. Neil等构建了IL-13启动子驱动的GFP报告基因小鼠，并据此鉴定出一群表型为lineage-T1/ST2+IL17BR+可表达IL-13从而介导Th2免疫应答的固有免疫细胞，并命名为nuocyte。IL-25和IL-33在体内可诱导nuocytes的扩增。nuocytes是蠕虫感染早期IL-13的主要来源细胞。在IL-25和IL-33信号同时缺失时，蠕虫感染不能诱导nuocytes的扩增，同时感染小鼠出现虫卵清除障碍。过继转移野生型的nuocytes可以补救IL-25和IL-33信号同时缺失所致的虫卵清除障碍，而过继转移IL-13-/- 小鼠的nuocytes并不能起到补救作用。
因此，固有免疫细胞nuocytes在Th2免疫应答中起到至关重要的作用。
（欧阳海峰 第四军医大学西京医院呼吸内科 710032 摘译）
（Nature. 2010;464(7293):1367-1370.）
Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity.
Neill DR, Wong SH, Bellosi A, Flynn RJ, Daly M, Langford TK, Bucks C, Kane CM, Fallon PG, Pannell R, Jolin HE, McKenzie AN.
Innate immunity provides the first line of defence against invading pathogens and provides important cues for the development of adaptive immunity. Type-2 immunity-responsible for protective immune responses to helminth parasites and the underlying cause of the pathogenesis of allergic asthma-consists of responses dominated by the cardinal type-2 cytokines interleukin (IL)4, IL5 and IL13. T cells are an important source of these cytokines in adaptive immune responses, but the innate cell sources remain to be comprehensively determined. Here, through the use of novel Il13-eGFP reporter mice, we present the identification and functional characterization of a new innate type-2 immune effector leukocyte that we have named the nuocyte. Nuocytes expand in vivo in response to the type-2-inducing cytokines IL25 and IL33, and represent the predominant early source of IL13 during helminth infection with Nippostrongylus brasiliensis. In the combined absence of IL25 and IL33 signalling, nuocytes fail to expand, resulting in a severe defect in worm expulsion that is rescued by the adoptive transfer of in vitro cultured wild-type, but not IL13-deficient, nuocytes. Thus, nuocytes represent a critically important innate effector cell in type-2 immunity.
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