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Item Epithelial barrier regulation, antigen sampling, and food allergy(Elsevier, 2022-09) Cook-Mills, Joan M.; Emmerson, Lauren N.; Microbiology and Immunology, School of MedicineFood allergy is often associated with development of atopic dermatitis. Atopic dermatitis is a chronic inflammatory skin condition with a strong association with skin barrier gene mutations. Loss-of-function mutations in skin barrier genes increase transepidermal water loss. Also, reduction of the skin barrier can be mediated by environmental exposures. In preclinical studies of mice with skin barrier disruption, exposure to allergens on the skin induces food allergy. Exposure to food allergens on the skin with coexposure of the skin to other environmental factors induces signals in the skin for activation of food allergy, allergen-specific IgE, and oral food–induced anaphylaxis. In contrast, oral food allergen consumption before skin exposure to food allergen induces tolerance to the food allergen. However, this induction of tolerance may be blocked if skin is exposed to environmental allergens at the time of initial oral food allergen consumption. Further studies are needed to address the mechanisms of induction of food allergy by coexposure of the skin to food allergens, aeroallergens, and other environmental factors. Furthermore, clinical studies are needed to determine the effects of food allergen on skin before skin development of atopic dermatitis.Item Oral Food Challenge Failures Among Foods Restricted Due to Atopic Dermatitis(Elsevier, 2018) Eapen, A. A.; Kloepfer, Kirsten M.; Leickly, Frederick E.; Slaven, James E.; Vitalpur, Girish; Pediatrics, School of MedicineBACKGROUND Recent studies have suggested that removing foods from the diet to manage atopic dermatitis (AD), based on positive allergy tests, may lead to immediate allergic reactions on reintroduction of that food. OBJECTIVE The purpose of this study was to examine the frequency of oral food challenge (OFC) failures among foods removed from the diet as suspected AD triggers, focusing on the five major food allergens in the US. METHODS OFCs to egg, milk, peanut, soy, and wheat, performed from 2008-14, at a children's hospital's allergy clinics, were reviewed. OFCs were offered based on history and laboratory values. Reasons for food avoidance were classified as food allergy (IgE-mediated reaction occurring within two hours); sensitization only (lack of introduction due to positive test results); and removal due to test results during AD evaluation. RESULTS There were 442 OFCs performed, with 89 failures (20.1%). Reasons for OFCs included a history of food allergy (320/442; 72.4%); food sensitization without any introduction (77/442; 17.4%); and AD (45/442; 10.2%). OFC failures among those who had food allergy (70/320; 21.9%); sensitization only (13/77; 16.9%); and suspected AD trigger (6/45; 13.3%) did not significantly differ (p=0.63). Wheat was more likely to be avoided than the other four foods for AD concerns (p<0.0001). CONCLUSION The frequency of OFC failure among those who removed foods suspected as AD triggers was 13.3%, indicating a loss of tolerance. Restriction of foods to manage AD must be done with caution and close monitoring.Item Phenotyping acute and chronic atopic dermatitis-like lesions in Stat6VT mice identifies a role for IL-33 in disease pathogenesis(Springer, 2018-04) DaSilva-Arnold, Sonia C.; Thyagarajan, Anita; Seymour, Leroy J.; Yi, Qiaofang; Bradish, Joshua R.; Al-Hassani, Mohammed; Zhou, Hongming; Perdue, Nikolajs J.; Nemmeth, Val; Krbanjevic, Aleksandar; Serezani, Ana P. M.; Olson, Matthew R.; Spandau, Dan F.; Travers, Jeffrey B.; Kaplan, Mark H.; Turner, Matthew J.; Dermatology, School of MedicineThe Stat6VT mouse model of atopic dermatitis (AD) is induced by T-cell-specific expression of a constitutively active form of the protein signal transducer and activator of transcription 6 (STAT6). Although AD-like lesions are known to develop in Stat6VT mice, this study was designed to determine if these mice develop acute and chronic phases of disease similar to humans. To address this, AD-like lesions from Stat6VT mice were harvested at two different timepoints relative to their onset. Lesions harvested within 1 week after development were defined as acute lesions, and those present for 1 month or more were defined as chronic lesions. Acute and chronic AD-like lesions from Stat6VT mice exhibited histologic findings and cytokine expression patterns similar to acute and chronic AD lesions in humans. Further analysis revealed increased levels of interleukin (IL)-33 transcripts in AD-like lesions compared to Stat6VT nonlesional and wild-type skin controls. Immunofluorescence also revealed increased numbers of IL-33+ keratinocytes in Stat6VT lesional skin and localized IL-33+ keratinocytes to a keratin 5+ subset. Furthermore, AD-like disease was more severe in IL-33-deficient Stat6VT mice compared to IL-33-sufficient Stat6VT mice. These studies suggest that Stat6VT mice can serve as a model of acute and chronic AD and that IL-33 may attenuate inflammation in this system.Item ResTORing barrier function in the skin(Elsevier, 2020-01) Wang, Jocelyn; Kaplan, Mark H.; Yang, Kai; Pediatrics, School of Medicine