Tanabe Kana, Kitagawa Eri, Wada Misaki, Haraguchi Atsushi, Orihara Kanami, Tahara Yu, Nakao Atsuhito, Shibata Shigenobu
Department of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
Waseda Institute for Advanced Study, Waseda University, Tokyo, Japan.
Sci Rep. 2015 Sep 30;5:14424. doi: 10.1038/srep14424.
The mammalian circadian clock controls many physiological processes that include immune responses and allergic reactions. Several studies have investigated the circadian regulation of intestinal permeability and tight junctions known to be affected by cytokines. However, the contribution of circadian clock to food allergy symptoms remains unclear. Therefore, we investigated the role of the circadian clock in determining the severity of food allergies. We prepared an ovalbumin food allergy mouse model, and orally administered ovalbumin either late in the light or late in the dark period under light-dark cycle. The light period group showed higher allergic diarrhea and weight loss than the dark period group. The production of type 2 cytokines, IL-13 and IL-5, from the mesenteric lymph nodes and ovalbumin absorption was higher in the light period group than in the dark period group. Compared to the dark period group, the mRNA expression levels of the tight junction proteins were lower in the light period group. We have demonstrated that increased production of type 2 cytokines and intestinal permeability in the light period induced severe food allergy symptoms. Our results suggest that the time of food antigen intake might affect the determination of the severity of food allergy symptoms.
哺乳动物的生物钟控制着许多生理过程,包括免疫反应和过敏反应。多项研究调查了已知受细胞因子影响的肠道通透性和紧密连接的昼夜节律调节。然而,生物钟对食物过敏症状的影响仍不清楚。因此,我们研究了生物钟在决定食物过敏严重程度中的作用。我们制备了卵清蛋白食物过敏小鼠模型,并在明暗循环条件下,于光照期晚期或黑暗期晚期经口给予卵清蛋白。光照期组比黑暗期组表现出更高的过敏性腹泻和体重减轻。光照期组肠系膜淋巴结中2型细胞因子IL-13和IL-5的产生以及卵清蛋白的吸收均高于黑暗期组。与黑暗期组相比,光照期组紧密连接蛋白的mRNA表达水平较低。我们已经证明,光照期2型细胞因子产生增加和肠道通透性增加会诱发严重的食物过敏症状。我们的结果表明,食物抗原摄入的时间可能会影响食物过敏症状严重程度的判定。