Sweat suppression promotes a Th2-biased sensitization to food allergens and anaphylaxis in an IL-6-dependent manner

Summary: Abstract Body: Background: Although sweat suppression is not generally considered to contribute to skin barrier dysfunction, sweating disturbance is frequently observed in atopic dermatitis (AD) patients with food allergy (FA) as well as in AD mouse models such as flaky tail mice. Our previous studies demonstrated that epicutaneous exposure of the BALB/c mouse footpad to the food allergen ovalbumin (OVA) results in sensitization to OVA and an anaphylaxis when the footpad skin is sweat-suppressed. Objectuve: In the present study, we investigated the relevance of sweat suppression in a mouse model of FA. We examined whether sweat suppression exhibits adjuvant-like effects by inducing innate cytokine responses. Results: Surprisingly, sweat suppression alone led to a robust induction of IL-6 from epidermis without tissue damage and this induction was abolished by exposure to high humidity (>80% relative humidity). This result indicates that sweat suppression has a strong impact on the ability to induce innate cytokine responses leading to FA. The ear swelling after OVA elicitation in OVA-sensitized mouse model facilitated by sweat suppression was completely abolished by exposure to high humidity during the sensitization process. Blockade of IL-6 signaling prior to OVA sensitization also led to markedly reduced OVA-IgE levels, indicating that sweat suppression may act as an adjuvant-like factor to promote OVA-IgE production through IL-6. Conclusion: Our data support the hypothesis that primary sensitization to food allergens in AD may occur through the sweat-disturbed, albeit normal-appearing, finger skin of infants who have not sufficiently developed their sweating function, considering that sweating responses in murine footpads are homologous to those in human fingers. Sweating disturbance may serve as an early biomarker predictive of AD and FA. Hironobu Ishimaru^{1, 2}, Takenobu Yamamoto¹, Yasuo Okamoto³, Yumi Aoyama¹ 1. Department of Dermatology, Kawasaki Ika Daigaku, Kurashiki, Okayama Prefecture, Japan. 2. Kyoto R&D Center, Maruho Kabushiki Kaisha, Osaka, Osaka Prefecture, Japan. 3. Department of Pharmacology, Kawasaki Ika Daigaku, Kurashiki, Okayama Prefecture, Japan. Adaptive and Auto-Immunity