Our daily rhythmicity is controlled by a circadian clock with a specific set of genes located in the suprachiasmatic nucleus in the hypothalamus. Mast cells (MCs) are major effector cells that play a protective role against pathogens and inflammation. MC distribution and activation are associated with the circadian rhythm via two major pathways, IgE/FcεRI‐ and IL‐33/ST2‐mediated signaling. Furthermore, there is a robust oscillation between clock genes and MC‐specific genes. Melatonin is a hormone derived from the amino acid tryptophan and is produced primarily in the pineal gland near the center of the brain, and histamine is a biologically active amine synthesized from the decarboxylation of the amino acid histidine by the L‐histidine decarboxylase enzyme. Melatonin and histamine are previously reported to modulate circadian rhythms by pathways incorporating various modulators in which the nuclear factor–binding near the κ light‐chain gene in B cells, NF‐κB, is the common key factor. NF‐κB interacts with the core clock genes and disrupts the production of pro‐inflammatory cytokine mediators such as IL‐6, IL‐13, and TNF‐α. Currently, there has been no study evaluating the interdependence between melatonin and histamine with respect to circadian oscillations in MCs. Accumulating evidence suggests that restoring circadian rhythms in MCs by targeting melatonin and histamine via NF‐κB may be promising therapeutic strategy for MC‐mediated inflammatory diseases. This review summarizes recent findings for circadian‐mediated MC functional roles and activation paradigms, as well as the therapeutic potentials of targeting circadian‐mediated melatonin and histamine signaling in MC‐dependent inflammatory diseases.

中文翻译：

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肥大细胞、松果体和昼夜节律之间的相互作用：组胺、褪黑激素和炎症介质之间的联系

我们的日常节律由生物钟控制，该生物钟具有一组位于下丘脑视交叉上核的特定基因。肥大细胞 (MC) 是主要的效应细胞，对病原体和炎症具有保护作用。MC 分布和激活通过 IgE/FcεRI 和 IL-33/ST2 介导的两个主要途径与昼夜节律相关。此外，时钟基因和 MC 特异性基因之间存在强烈的振荡。褪黑激素是一种源自氨基酸色氨酸的激素，主要在大脑中心附近的松果体中产生，组胺是一种具有生物活性的胺，由 L-组氨酸脱羧酶对氨基酸组氨酸的脱羧作用合成。褪黑激素和组胺之前被报道通过结合各种调节剂的途径调节昼夜节律，其中与 B 细胞中 κ 轻链基因附近的核因子结合，NF-κB 是共同的关键因素。NF-κB 与核心时钟基因相互作用并破坏促炎细胞因子介质如 IL-6、IL-13 和 TNF-α 的产生。目前，还没有研究评估褪黑激素和组胺之间在 MC 昼夜节律振荡方面的相互依赖性。越来越多的证据表明，通过 NF-κB 靶向褪黑激素和组胺来恢复 MC 的昼夜节律可能是 MC 介导的炎症性疾病的有希望的治疗策略。本综述总结了昼夜节律介导的 MC 功能作用和激活范式的最新发现，