TICAM-1 is dispensable in STING-mediated innate immune responses in myeloid immune cells
TICAM-1 is dispensable in STING-mediated innate immune responses in myeloid immune cells
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TICAM-1 在 STING 介导的骨髓免疫细胞先天免疫反应中是可有可无的
DOI：
10.1016/j.bbrc.2018.04.035
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发表时间：
2018
影响因子：
3.1
通讯作者：
Seya Tsukasa
中科院分区：
文献类型：
--
作者：
Takashima Ken;Oshiumi Hiroyuki;Matsumoto Misako;Seya Tsukasa
干扰素基因刺激物 (STING) 是响应胞质 DNA 产生 I 型干扰素 (IFN) 和其他炎症细胞因子的重要分子。 STING 有助于宿主防御感染和抗肿瘤反应。先前的报告表明，含有 Toll-IL-1 受体的接头分子 1 (TICAM-1) 需要 STING 信号传导，该接头分子已通过小鼠胚胎成纤维细胞鉴定为 TLR3 接头分子。在这里，我们证明 TICAM-1 不会影响 STING 介导的先天免疫反应，因为在骨髓来源或脾髓细胞中观察到 IFN-β、IL-6 和 CCL5 的 mRNA 表达水平增加。此外，在脾脏 CD11c + DC 上检测到 STING 配体增强的共刺激分子表达，包括 CD80、CD86 和 CD40，甚至在 Ticam-1 缺陷小鼠中也是如此。我们的结果表明，STING 介导的先天免疫反应和树突状细胞成熟不需要骨髓系免疫细胞中的 TICAM-1。 TICAM-1 普遍表达，甚至在不表达 TLR3 的细胞类型中也是如此。因此，TICAM-1 可能具有不同的功能，具体取决于细胞类型和信号传导目的。
Stimulator of interferon genes (STING) is an essential molecule for the production of type I interferon (IFN), and other inflammatory cytokines, in response to cytosolic DNA. STING contributes to host defense against infection and anti-tumor responses. Previous reports have demonstrated that STING signaling is required by the adaptor Toll-IL-1 receptor-containing adaptor molecule-1 (TICAM-1), which has been identified as a TLR3-adaptor molecule using mouse embryonic fibroblasts. Here, we demonstrate that TICAM-1 does not affect STING-mediated innate immune responses, as increases in the mRNA expression levels of IFN-β, IL-6, and CCL5 were observed in bone marrow-derived or splenic myeloid cells. Moreover, STING ligand-enhanced co-stimulatory molecule expression, including CD80, CD86, and CD40, was detected on splenic CD11c + DCs, even inTicam-1-deficient mice. Our results suggest that STING-mediated innate immune responses and dendritic cell maturation do not require TICAM-1 in myeloid lineage immune cells. TICAM-1 is ubiquitously expressed, even in cell types which do not express TLR3. Therefore, TICAM-1 may possess different functions depending on cell type and signaling purposes.