After their migration to the lymph nodes, activated DCs polarize CD4 T cells into Th2 cells that themselves secrete IL4, IL5, and IL13, thereby stimulating the production of IgE and amplifying the type 2 inflammatory response ( Deckers et al., 2017a Akdis et al., 2020). These soluble mediators stimulate the production of IL4, IL5, and IL13 by type 2 innate-like lymphoid cells (ILCs) and basophils, and the activation of dendritic cells (DCs) ( Deckers et al., 2017a Akdis et al., 2020). In the skin and lungs, allergens trigger the secretion by keratinocytes or epithelial cells of alarmins, such as thymic stromal lymphopoietin (TSLP) ( Deckers et al., 2017a Akdis et al., 2020). Type 2 allergic responses result from dysregulated immune responses mediated mainly by IL4, IL5, and IL13. In particular, whether dietary metabolites that activate the aryl hydrocarbon receptor (AhR) influence type 2 allergic responses remains unclear. However, the impact of individual nutrients and the molecular mechanisms involved remain incompletely understood. Dietary compounds can modulate immune cells homeostasis and inflammatory immune responses ( Wu et al., 2018), affecting in particular the susceptibility to allergy ( Julia et al., 2015). Editor's evaluationĭevelopment of immune-mediated diseases is affected by numerous environmental factors, including nutrition. 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. In particular, we evidenced TGF-β hyperproduction in the skin of mice deprived of dietary AhR ligands, explaining Langerhans cell retention.

Mechanistically, dietary AhR ligands regulated the inflammatory profile of epidermal cells, without affecting barrier function. 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. This phenomenon was tissue-specific as airway allergy was unaffected by the diet. In cutaneous papain-induced allergy, we found that lack of dietary AhR ligands exacerbates allergic responses. Here, we addressed the influence on allergic responses of dietary agonists of aryl hydrocarbon receptor (AhR). However, the mechanisms involved remain incompletely understood. Dietary compounds can affect the development of inflammatory responses at distant sites.

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