Small intestinal immune-environmental changes induced by oral tolerance inhibit experimental atopic dermatitis

Abstract

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.

Oxidative Stress and Gut Microbiome in Inflammatory Skin Diseases

“…A study from Gachon University developed a murine model of AD by the repeated epicutaneous exposure of tape-stripped skin to ovalbumin. It revealed that the induction of oral tolerance protects mice from AD-like dermatitis and inhibits the increase in small intestinal eosinophils and dysregulated alterations in the gut microbiome ( Um et al, 2021 ). Combining previous studies of AD mice, it may suggest that gut bacterial strains can provide stimulation and promote maturation of the infant immune system.…”

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