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Background: Food allergy (FA) and atopic dermatitis (AD) are common conditions that often present in the first year of life. Identification of underlying mechanisms and environmental determinants of FA and AD is essential to develop and implement effective prevention and treatment strategies. Objectives: We sought to describe the design of the Systems Biology of Early Atopy (SunBEAm) birth cohort., Methods: Funded by the National Institute of Allergy and Infectious Diseases (NIAID) and administered through the Consortium for Food Allergy Research (CoFAR), SunBEAm is a US population-based, multicenter birth cohort that enrolls pregnant mothers, fathers, and their newborns and follows them to 3 years. Questionnaire and biosampling strategies were developed to apply a systems biology approach to identify environmental, immunologic, and multiomic determinants of AD, FA, and other allergic outcomes., Results: Enrollment is currently underway. On the basis of an estimated FA prevalence of 6%, the enrollment goal is 2500 infants. AD is defined on the basis of questionnaire and assessment, and FA is defined by an algorithm combining history and testing. Although any FA will be recorded, we focus on the diagnosis of egg, milk, and peanut at 5 months, adding wheat, soy, cashew, hazelnut, walnut, codfish, shrimp, and sesame starting at 12 months. Sampling includes blood, hair, stool, dust, water, tape strips, skin swabs, nasal secretions, nasal swabs, saliva, urine, functional aspects of the skin, and maternal breast milk and vaginal swabs., Conclusions: The SunBEAm birth cohort will provide a rich repository of data and specimens to interrogate mechanisms and determinants of early allergic outcomes, with an emphasis on FA, AD, and systems biology., Competing Interests: DISCLOSURE STATEMENT Funded by the following grants from NIAID/National Institutes of Health (NIH): UM2AI130836, UM1AI130838, UM1AI130839, UM1AI130781, UM1AI130936, UM1AI130936, UM1AI130780, UM1AI130934, UM1AI130570, UM1AI173380, UM1AI151958, and UM1AI109565. The authorships of P.C.F., A.T., W.D., S.H., and S.P. do not constitute endorsement by the National Institute of Allergy and Infection Diseases, the National Institutes of Health, or any other agency of the United States government. Disclosure of potential conflict of interest: C. Keet reports royalties from UpToDate. S. H. Sicherer reports royalty payments from UpToDate and Johns Hopkins University Press; grants to his institution from NIAID, Food Allergy Research and Education, and Pfizer; personal fees from the American Academy of Allergy, Asthma & Immunology; and deputy editorship of the Journal of Allergy and Clinical Immunology: In Practice, outside of the submitted work. C. M. Davis reports grant support from NIAID/NIH, Immune Tolerance Network, DBV Technologies, Regeneronm Pfizer, and Allergenis; and consultant for Aimmune. S. Anvari reports research support from NIAID/NIH and DBV Technologies; and serves on the advisory board for Sanofi. M. Groetch receives royalties from UpToDate, FARE, and the Academy of Nutrition and Dietetics; serves on the medical advisory board of IFPIES, as senior advisor to FARE, and as health sciences advisor for APFED; and sits on the editorial board of Journal of Food Allergy. W. Shreffler reports royalty payments from UpToDate; grants to his institution from NIAID and Food Allergy Research and Education; sponsored research funds from Aimune, Angany Therapeutics, Moderna, Regeneron, Vedanta Biosciences and consultant fees from Aimmune, ALK, Allergy Therapeutics, Novartis, Regeneron, and Sanofi. Dr. Leung reports support from Sanofi, Genentech, Leo Pharma, and Incyte. H. Kim reports advisory board for ALK, Kenota Health, and Ukko Inc; consultant for Allergy Therapeutics Ltd, Belhaven Biopharma, Duke Clinical Research Institute, Genentech, and Nutricia. J. Wang receives research support from NIAID, Aimmune, DBV Technologies, and Regeneron; and consultancy fees from ALK Abello and Jubilant HollisterStier. R. A. Wood reports research support from NIAID, Aimmune, Astellas, DBV, FARE, Genentech, HAL-Allergy, Novartis, and Regeneron; and royalties from UpToDate. The rest of the authors declare that they have no relevant conflicts of interest.

Background: Staphylococcus (S) aureus colonization is known to cause skin barrier disruption in atopic dermatitis (AD) patients. However, it has not been studied how S. aureus induces aberrant epidermal lipid composition and skin barrier dysfunction., Methods: Skin tape strips (STS) and swabs were obtained from 24 children with AD (6.0 ± 4.4 years) and 16 healthy children (7.0 ± 4.5 years). Lipidomic analysis of STS samples was performed by mass spectrometry. Skin levels of methicillin-sensitive and methicillin-resistant S. aureus (MSSA and MRSA) were evaluated. The effects of MSSA and MRSA were evaluated in primary human keratinocytes (HEKs) and organotypic skin cultures., Results: AD and organotypic skin colonized with MRSA significantly increased the proportion of lipid species with nonhydroxy fatty acid sphingosine ceramide with palmitic acid ([N-16:0 NS-CER], sphingomyelins [16:0-18:0 SM]), and lysophosphatidylcholines [16:0-18:0 LPC], but significantly reduced the proportion of corresponding very long-chain fatty acids (VLCFAs) species (C22-28) compared to the skin without S. aureus colonization. Significantly increased transepidermal water loss (TEWL) was found in MRSA-colonized AD skin. S. aureus indirectly through interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, and IL-33 inhibited expression of fatty acid elongase enzymes (ELOVL3 and ELOVL4) in HEKs. ELOVL inhibition was more pronounced by MRSA and resulted in TEWL increase in organotypic skin., Conclusion: Aberrant skin lipid profiles and barrier dysfunction are associated with S. aureus colonization in AD patients. These effects are attributed to the inhibition of ELOVLs by S. aureus-induced IL-1β, TNF-α, IL-6, and IL-33 seen in keratinocyte models and are more prominent in MRSA than MSSA., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Children born in the fall and winter are at increased risk for developing atopic dermatitis and food allergy. Because these seasons are associated with low temperatures, we hypothesized that exposure to low temperatures may compromise keratinocyte differentiation and contribute to skin barrier dysfunction., Objective: We examined whether low temperature causes skin barrier dysfunction., Methods: Primary human epidermal keratinocytes (HEK) were differentiated in 1.3 mmol CaCl 2 media and cultured at different temperatures. The cells were transfected with transient receptor potential cation channel subfamily V member 1 (TRPV1) or STAT3 small interfering RNA (siRNA) to examine the effects of these gene targets in HEK exposed to low temperature. Gene expression of TRPV1, epidermal barrier proteins, and keratinocyte-derived cytokines were evaluated. Organotypic skin equivalents were generated using HEK transfected with control or TRPV1 siRNA and grown at 25°C or 37°C. Transepidermal water loss (TEWL) and levels of epidermal barrier proteins were evaluated., Results: Filaggrin (FLG) and loricrin (LOR) expression, but not keratin (KRT)-1 and KRT-10 expression, was downregulated in HEK incubated at 25°C, while TRPV1 silencing increased intracellular Ca 2+ influx (keratinocyte differentiation signal) and enhanced the expression of epidermal differentiation proteins. IL-1β and thymic stromal lymphopoietin induced by low temperature inhibited FLG expression in keratinocytes through the TRPV1/STAT3 pathway. Moreover, low temperature-mediated inhibition of FLG and LOR was recovered, and TEWL was decreased in organotypic skin transfected with TRPV1 siRNA., Conclusion: TRPV1 is critical in low temperature-mediated skin barrier dysfunction. Low temperature exposure induced thymic stromal lymphopoietin, an alarmin implicated in epicutaneous allergen sensitization., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

As the incidence of atopic conditions continues to increase, emphasis has been placed on understanding the origin of allergy with hope that prevention measures can be achieved. The perinatal environment is important for this understanding, given that both the immune system and microbiome start forming prenatally. Maternal exposure can greatly impact on fetal health. Additionally, the dysfunctional epithelial barrier is influential in allowing allergens and irritants to penetrate the skin or mucosa, leading to the release of proinflammatory cytokines and mediators to drive type 2 tissue inflammation and the onset of allergy. There are numerous factors related to skin, airway, and gut epithelial barriers dysfunction, and genetic predispositions are also present. Comprehensive birth cohort studies and further mechanistic studies will be keys to understanding the origin of allergy., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2022 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)