IL-21 UP-Regulates the expression of genes associated with innate immunity and Th1 response
IL-21 UP-Regulates the expression of genes associated with innate immunity and Th1 response
复制标题
DOI：
10.4049/jimmunol.169.7.3600
复制
发表时间：
2002-10-01
影响因子：
4.4
通讯作者：
Matikainen, S
中科院分区：
文献类型：
--
作者：
Strengeil, M;Sareneva, T;Matikainen, S
IL-21是最近表征的调节NK和T细胞功能的T细胞衍生的细胞因子。IL-21 R与IL-2、IL-4、IL-7、IL-9和IL-15的受体共享共同的γ链（γ（c））。尽管γ（c）相同，但这些细胞因子对不同细胞具有不同的作用。在这项研究中，我们研究了IL-15和IL-21诱导的基因表达的人原代NK和T细胞和NK-92细胞系。IL-15和IL-21均快速诱导IFN-γ、T-bet、IL-2 R α、IL-12 R β 2、IL-18 R和髓样分化因子88（MyD 88）的mRNA合成，这些基因在激活先天免疫和Th 1应答中很重要。IL-15诱导STAT 5 DNA与IL-2 R α IFN-γ激活序列（GAS）、MyD 88 GAS和c-sis诱导元件结合，而IL-21诱导STAT 3 DNA与MyD 88 GAS和c-sis诱导元件结合。IL-21诱导的STAT 3活化通过免疫沉淀和用抗磷酸酪氨酸Ab的Western印迹来验证。此外，用IL-15或IL-21预处理NK-92细胞强烈增强IL-12诱导的STAT 4 DNA与IL-2 R α GAS的结合。NK细胞中IFN-γ、T-bet、IL-12 R β 2和IL-18 R基因表达的诱导，沿着STAT 3活化，表明IL-21参与先天免疫应答的活化。此外，这些基因在T细胞中的转录增强也确立了IL-21在Th 1应答中的重要作用。
IL-21 is a recently characterized T cell-derived cytokine that regulates NK and T cell function. IL-21R shares the common gamma-chain (gamma(c)) with the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15. Despite the same gamma(c), these cytokines have different effects on diverse cells. In this study, we have studied IL-15- and IL-21-induced gene expression in human primary NK and T cells and the NK-92 cell line. Both IL-15 and IL-21 rapidly induced mRNA synthesis for IFN-gamma, T-bet, IL-2Ralpha, IL-12Rbeta2, IL-18R, and myeloid differentiation factor 88 (MyD88), the genes that are important in activating innate immunity and Th1 response. IL-15 induced STAT5 DNA binding to the IL-2Ralpha IFN-gamma-activated sequence (GAS), MyD88 GAS, and c-sis-inducible elements, whereas IL-21 induced STAT3 DNA binding to MyD88 GAS and c-sis-inducible elements. IL-21-induced STAT3 activation was verified by immunoprecipitation and Western blotting with anti-phosphotyrosine Ab. In addition, pretreatment of NK-92 cells with IL-15 or IL-21 strongly enhanced IL-12-induced STAT4 DNA binding to IL-2Ralpha GAS. The induction of IFN-gamma, T-bet, IL-12Rbeta2, and IL-18R gene expression in NK cells, along with STAT3 activation, suggests that IL-21 is involved in the activation of innate immune responses. Moreover, the enhanced transcription of these genes in T cells establishes a significant role for IL-21 also in the Th1 response.