状态4
白细胞介素12
生物
细胞因子
状态5
白细胞介素21
干扰素γ
T细胞
白细胞介素18
STAT1
分子生物学
免疫系统
细胞生物学
斯达
信号转导
车站3
免疫学
细胞毒性T细胞
体外
生物化学
作者
Mari Strengell,Sampsa Matikainen,Jukka Sirén,Anne Lehtonen,Don Foster,Ilkka Julkunen,Timo Sareneva
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2003-06-01
卷期号:170 (11): 5464-5469
被引量:372
标识
DOI:10.4049/jimmunol.170.11.5464
摘要
Abstract NK and T cell-derived IFN-γ is a key cytokine that stimulates innate immune responses and directs adaptive T cell response toward Th1 type. IL-15, IL-18, and IL-21 have significant roles as activators of NK and T cell functions. We have previously shown that IL-15 and IL-21 induce the expression of IFN-γ, T-bet, IL-12Rβ2, and IL-18R genes both in NK and T cells. Now we have studied the effect of IL-15, IL-18, and IL-21 on IFN-γ gene expression in more detail in human NK and T cells. IL-15 clearly activated IFN-γ mRNA expression and protein production in both cell types. IL-18 and IL-21 enhanced IL-15-induced IFN-γ gene expression. IL-18 or IL-21 alone induced a modest expression of the IFN-γ gene but a combination of IL-21 and IL-18 efficiently up-regulated IFN-γ production. We also show that IL-15 activated the binding of STAT1, STAT3, STAT4, and STAT5 to the regulatory sites of the IFN-γ gene. Similarly, IL-21 induced the binding of STAT1, STAT3, and STAT4 to these elements. IL-15- and IL-21-induced STAT1 and STAT4 activation was verified by immunoprecipitation with anti-phosphotyrosine Abs followed by Western blotting with anti-STAT1 and anti-STAT4 Abs. IL-18 was not able to induce the binding of STATs to IFN-γ gene regulatory sites. IL-18, however, activated the binding of NF-κB to the IFN-γ promoter NF-κB site. Our results suggest that both IL-15 and IL-21 have an important role in activating the NK cell-associated innate immune response.
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