Nuclear receptors (NRs) rapidly activate/repress gene expression to detour immune responses and allow tissue adaptation to constant environmental changes. However, the effect of combined NRs in the immune system is often unclear due to the lack of reliable experimental models that recapitulate the complex interaction between NRs in vivo. Here, we used the zebrafish to investigate the immunological outcome of combining the activation of retinoic acid receptor (RAR), liver X receptor (LXR) and the cytoplasmic sensor aryl hydrocarbon receptor (AHR). Although simultaneous activation did not affect the expression of respective bona-fide target genes, RAR-induced il17a/f3 was antagonized by LXR and AHR, whereas il22 was antagonized by AHR but not LXR. In addition, RA decreased il10 expression, which was further decreased by LXR activation. Thus, using combinatorial NR activation in zebrafish larvae, we show that LXR antagonizes the expression of selected RA-induced cytokines and provide a strategy to tailor the cytokine milieu.

中文翻译：

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维甲酸诱导的细胞因子在斑马鱼中被肝X受体激活选择性调节。

核受体（NRs）迅速激活/抑制基因表达以绕过免疫反应，并使组织适应不断变化的环境。然而，由于缺乏可靠的实验模型来概括体内NRs之间的复杂相互作用，因此组合NRs在免疫系统中的作用通常尚不清楚。在这里，我们使用斑马鱼来研究结合视黄酸受体（RAR），肝X受体（LXR）和细胞质传感器芳烃受体（AHR）激活的免疫学结果。尽管同时激活并不影响相应的真正靶基因的表达，但RAR诱导的il17a / f3被LXR和AHR拮抗，而il22被AHR而非LXR拮抗。此外，RA降低了il10表达，而LXR激活进一步降低了il10表达。从而，