Department of Health Science and Technology, Gachon Advanced Institute for Health Science & Technology, Gachon University, Incheon, 21999, South Korea.
Department of Dermatology, Gachon Gil Medical Center, College of Medicine, Gachon University, Incheon, 21565, Korea.
Cell Death Dis. 2021 Mar 4;12(3):243. doi: 10.1038/s41419-021-03534-w.
Atopic dermatitis is a chronic skin inflammatory disease mediated by Th2-type immune responses. Although intestinal immune responses have been shown to play a critical role in the development or prevention of atopic dermatitis, the precise influence of intestinal immunity on atopic dermatitis is incompletely understood. We show here that orally tolerized mice are protected from experimental atopic dermatitis induced by sensitization and epicutaneous (EC) challenge to ovalbumin. Although the expression of Th2-type cytokines in the small intestine of orally tolerized and EC-challenged mice did not change significantly, these mice showed decreased inflammatory responses in the small intestine with restoration of microbial change elicited by the EC challenge. Interestingly, an increase in small intestinal eosinophils was observed with the EC challenge, which was also inhibited by oral tolerance. The role of small intestinal eosinophils and microbiota in the pathogenesis of experimental atopic dermatitis was further substantiated by decreased inflammatory mediators in the small intestine and attenuated Th2-type inflammation in the skin of eosinophil-deficient and microbiota-ablated mice with EC challenges. Based on these data, we propose that the bidirectional interaction between the skin and the intestine has a role in the pathogenesis of atopic dermatitis and that modulation of the intestinal microenvironments could be a therapeutic approach to atopic dermatitis.
特应性皮炎是一种由 Th2 型免疫应答介导的慢性皮肤炎症性疾病。尽管肠道免疫应答已被证明在特应性皮炎的发生或预防中起着关键作用，但肠道免疫对特应性皮炎的确切影响尚不完全清楚。我们在这里表明，经口服耐受处理的小鼠可免受卵清蛋白致敏和经皮（EC）挑战诱导的实验性特应性皮炎的影响。尽管口服耐受和 EC 挑战小鼠小肠中 Th2 型细胞因子的表达没有明显变化，但这些小鼠的小肠炎症反应减轻，同时恢复了 EC 挑战引起的微生物变化。有趣的是，EC 挑战会引起小肠嗜酸性粒细胞增加，而口服耐受也会抑制这种增加。EC 挑战时，小肠嗜酸性粒细胞和微生物群在实验性特应性皮炎发病机制中的作用进一步得到证实，因为在缺乏嗜酸性粒细胞和经 EC 挑战的微生物群缺失的小鼠中，小肠中的炎症介质减少，皮肤中的 Th2 型炎症减轻。基于这些数据，我们提出皮肤和肠道之间的双向相互作用在特应性皮炎的发病机制中起作用，并且调节肠道微环境可能是治疗特应性皮炎的一种方法。
