Significant role for IRF3 in both T cell and APC effector functions during T cell responses.

Significant role for IRF3 in both T cell and APC effector functions during T cell responses.
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DOI:
10.1016/j.cellimm.2016.08.015
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发表时间:
2016-12
影响因子:
4.3
通讯作者:
Petro TM
Petro TM
中科院分区:
医学4区
文献类型:
--
作者:
Guinn Z;Lampe AT;Brown DM;Petro TM

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干扰素调节因子(IRF)3是天然免疫应答过程中的重要转录因子。在这里,我们展示了IRF3在适应性T细胞免疫反应中也有作用。IRF3KO小鼠来源的树突状细胞(DC)或T细胞在体外T细胞反应中的干扰素-γ、IL-17和颗粒酶B(GrB)的表达均受到抑制。出乎意料的是,IRF3依赖的NK激活分子(INAM)是DC天然免疫应答的NK细胞激活因子,在T细胞应答过程中被诱导。此外,应答T细胞的上清以IRF3依赖的方式诱导RAW264.7巨噬细胞系的ISG54。此外,加入抗干扰素-γ抑制了培养上清液对ISG54的诱导,重组干扰素-γ促进了ISG54的表达。因此,APC和T细胞中的IRF3对于最佳的T细胞效应器功能和T细胞影响APC天然免疫功能的能力是必需的。
Interferon Regulatory Factor (IRF)3 is a crucial transcription factor during innate immune responses. Here we show IRF3 also has a role in adaptive T cell immune responses. Expression of IFN-γ, IL-17, and Granzyme B (GrB) during in vitro T cell responses was impaired when either dendritic cells (DCs) or T cells were derived from IRF3KO mice. Unexpectedly, IRF3–dependent NK-activating molecule (INAM), which is an NK cell activating factor of the DC innate immune response, was induced during the T cell response. Additionally, supernatants from responding T cells induced ISG54 in the RAW264.7 macrophage cell line in an IRF3 dependent manner. Moreover, addition of anti-IFN-γ prevented supernatant induction of ISG54 and recombinant IFN-γ stimulated ISG54 expression. Thus, IRF3 in APCs and T cells is required for optimal T-cell effector function and the ability of T cells to influence innate immune function of APCs.
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