Institut Curie, PSL Research University, INSERM, U932, Paris, France.
Institut Curie, PSL Research University, Plateforme de Pathologie Expérimentale, Paris, France.
Elife. 2023 May 16;12:e86413. doi: 10.7554/eLife.86413.
Dietary compounds can affect the development of inflammatory responses at distant sites. However, the mechanisms involved remain incompletely understood. Here, we addressed the influence on allergic responses of dietary agonists of aryl hydrocarbon receptor (AhR). In cutaneous papain-induced allergy, we found that lack of dietary AhR ligands exacerbates allergic responses. This phenomenon was tissue-specific as airway allergy was unaffected by the diet. In addition, lack of dietary AhR ligands worsened asthma-like allergy in a model of 'atopic march.' Mice deprived of dietary AhR ligands displayed impaired Langerhans cell migration, leading to exaggerated T cell responses. Mechanistically, dietary AhR ligands regulated the inflammatory profile of epidermal cells, without affecting barrier function. In particular, we evidenced TGF-β hyperproduction in the skin of mice deprived of dietary AhR ligands, explaining Langerhans cell retention. Our work identifies an essential role for homeostatic activation of AhR by dietary ligands in the dampening of cutaneous allergic responses and uncovers the importance of the gut-skin axis in the development of allergic diseases.
膳食化合物可以影响远处部位炎症反应的发展。然而，相关的机制仍不完全清楚。在这里，我们研究了芳基烃受体（AhR）的膳食激动剂对过敏反应的影响。在皮肤木瓜蛋白酶诱导的过敏中，我们发现缺乏膳食 AhR 配体可加重过敏反应。这种现象具有组织特异性，因为气道过敏不受饮食影响。此外，缺乏膳食 AhR 配体在“特应性进展”模型中加重了哮喘样过敏。缺乏膳食 AhR 配体的小鼠显示出朗格汉斯细胞迁移受损，导致 T 细胞反应过度。从机制上讲，膳食 AhR 配体调节表皮细胞的炎症特征，而不影响屏障功能。特别是，我们证明了缺乏膳食 AhR 配体的小鼠皮肤中 TGF-β的过度产生，这解释了朗格汉斯细胞的滞留。我们的工作确定了膳食配体对 AhR 的内稳态激活在抑制皮肤过敏反应中的重要作用，并揭示了肠道-皮肤轴在过敏疾病发展中的重要性。
