T Lymphocyte-Dependent and -Independent Regulation of Cxcl8 Expression in Zebrafish Intestines
T Lymphocyte-Dependent and -Independent Regulation of Cxcl8 Expression in Zebrafish Intestines
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DOI：
10.4049/jimmunol.1301865
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发表时间：
2014-01-01
影响因子：
4.4
通讯作者：
Nieuwenhuis, Edward E. S.
中科院分区：
文献类型：
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作者：
Brugman, Sylvia;Witte, Merlijn;Nieuwenhuis, Edward E. S.
CXCL8 是一种有效的中性粒细胞募集趋化因子。 CXCL8 由多种先天免疫细胞产生，包括中性粒细胞、巨噬细胞以及上皮细胞。尽管之前认为仅是这些细胞中 TLR 信号传导的结果，但最近的报告表明 T 细胞衍生的细胞因子也在上皮细胞中诱导 CXCL8。同样，我们观察到，在小肠结肠炎的早期阶段，T 细胞抑制减少了肠道中 CXCL8 功能性小鼠同源物的产生。在这项研究中，我们专门研究了适应性细胞是否有助于肠道中先天的 cxcl8 表达。为此，我们使用斑马鱼作为我们的模型系统。与缺乏 CXCL8 的小鼠模型不同，斑马鱼有两种 CXCL8 趋化因子，它们在急性炎症刺激后都会升高并招募中性粒细胞。此外，斑马鱼依次发展先天性免疫和适应性免疫，从而能够在缺乏适应性免疫（3周龄）的情况下分析肠道 cxcl8 表达。在这项研究中，我们发现肠道 cxcl8-l1 而不是 cxcl8-l2 表达在稳态条件下受 T 淋巴细胞调节。相反，尤其是在肠道炎症期间，cxcl8-l1 表达上调，与 T 淋巴细胞的存在无关。此外，我们发现人CXCL8能够诱导斑马鱼肠道中性粒细胞募集和cxcl8-l1表达，证明斑马鱼可以用作研究CXCL8功能和调节的模型。总之，这些数据提供的证据表明，Cxcl8-l1 和 Cxcl8-l2 在稳态和炎症过程中通过 T 淋巴细胞依赖性和非依赖性机制进行差异调节。
CXCL8 is a potent neutrophil recruiting chemokine. CXCL8 is produced by several innate immune cells, including neutrophils, macrophages, as well as epithelial cells. Although previously considered only to be produced as a result of TLR signaling in these cells, recent reports show that T cell-derived cytokines also induce CXCL8 in epithelial cells. Likewise, we observed that T cell inhibition diminished intestinal production of functional mouse homologs of CXCL8 in the early phase of enterocolitis. In this study, we specifically investigated whether adaptive cells contribute to innate cxcl8 expression in the intestines. To this end, we used the zebrafish as our model system. Unlike murine models that lack CXCL8, zebrafish have two CXCL8 chemokines that are both elevated after an acute inflammatory stimulus and recruit neutrophils. Furthermore, zebrafish develop innate and adaptive immunity sequentially, enabling analysis of intestinal cxcl8 expression in the absence (3 wk of age) of adaptive immunity. In this study, we show that intestinal cxcl8-l1 but not cxcl8-l2 expression is regulated by T lymphocytes under homeostatic conditions. In contrast, during intestinal inflammation especially, cxcl8-l1 expression is upregulated independent of T lymphocyte presence. Furthermore, we show that human CXCL8 is able to induce intestinal zebrafish neutrophil recruitment and cxcl8-l1 expression, demonstrating that zebrafish can be used as a model to study CXCL8 function and regulation. In conclusion, these data provide evidence that Cxcl8-l1 and Cxcl8-l2 are differentially regulated via T lymphocyte-dependent and -independent mechanisms during homeostasis and inflammation.