Interleukin-10 Is Produced by a Specific Subset of Taste Receptor Cells and Critical for Maintaining Structural Integrity of Mouse Taste Buds
Interleukin-10 Is Produced by a Specific Subset of Taste Receptor Cells and Critical for Maintaining Structural Integrity of Mouse Taste Buds
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DOI：
10.1523/jneurosci.3074-13.2014
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发表时间：
2014-02-12
影响因子：
5.3
通讯作者：
Wang, Hong
中科院分区：
文献类型：
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作者：
Feng, Pu;Chai, Jinghua;Wang, Hong
尽管炎症反应是抵御病原体的关键组成部分，但太多的炎症是有害的。已经进化出调节炎症的机制，包括抗炎细胞因子白介素10(IL-10)的调节。此前，我们已经证明味蕾表达与先天免疫反应有关的各种分子，包括促炎细胞因子肿瘤坏死因子(TNF)。在这里，使用一种报告的小鼠品系，我们表明味觉细胞也表达抗炎细胞因子IL-10。值得注意的是，IL-10只由特定的味觉细胞亚群产生，这与小鼠环状和叶状味蕾中产生肿瘤坏死因子的细胞不同：IL-10仅在表达G蛋白Gustducin的苦味受体细胞中表达，而肿瘤坏死因子则像先前报道的那样在甜味和鲜味受体细胞中表达。相比之下，IL-10受体的配体结合亚单位IL-10R1主要由产生肿瘤坏死因子的细胞表达，这表明了一种新的细胞层次结构，用于调节肿瘤坏死因子的产生和在味蕾中的作用。作为对炎症挑战的反应，味觉细胞在体内和体外都可以增加IL-10的表达。这些发现表明，味蕾使用不同的味觉感受器细胞群，这些细胞与甜味/鲜味和苦味的接收重合，以调节局部炎症反应，这一现象以前从未报道过。此外，IL-10缺乏导致小鼠味蕾的数量和大小以及每个味蕾的味觉感受器细胞数量显著减少，这表明IL-10在维持周围味觉系统的结构完整性方面发挥着关键作用。
Although inflammatory responses are a critical component in defense against pathogens, too much inflammation is harmful. Mechanisms have evolved to regulate inflammation, including modulation by the anti-inflammatory cytokine interleukin-10 (IL-10). Previously we have shown that taste buds express various molecules involved in innate immune responses, including the proinflammatory cytokine tumor necrosis factor (TNF). Here, using a reporter mouse strain, we show that taste cells also express the anti-inflammatory cytokine IL-10. Remarkably, IL-10 is produced by only a specific subset of taste cells, which are different from the TNF-producing cells in mouse circumvallate and foliate taste buds: IL-10 expression was found exclusively in the G-protein gustducin-expressing bitter receptor cells, while TNF was found in sweet and umami receptor cells as reported previously. In contrast, IL-10R1, the ligand-binding subunit of the IL-10 receptor, is predominantly expressed by TNF-producing cells, suggesting a novel cellular hierarchy for regulating TNF production and effects in taste buds. In response to inflammatory challenges, taste cells can increase IL-10 expression both in vivo and in vitro. These findings suggest that taste buds use separate populations of taste receptor cells that coincide with sweet/umami and bitter taste reception to modulate local inflammatory responses, a phenomenon that has not been previously reported. Furthermore, IL-10 deficiency in mice leads to significant reductions in the number and size of taste buds, as well as in the number of taste receptor cells per taste bud, suggesting that IL-10 plays critical roles in maintaining structural integrity of the peripheral gustatory system.