Effects of TNCB sensitization in DS-Nh mice, serving as a model of atopic dermatitis, in comparison with NC/Nga mice

BACKGROUND: It has been predicted that a type-1 and type-2 helper T cell (Th1/Th2) imbalance exists in atopic dermatitis (AD). In DS-Nh mice, an AD mouse model, Staphylococcus aureus increases on the skin surface. OBJECTIVE: To investigate whether the Th1-dominant response has an influence on the development of AD, we induced chronic allergic hypersensitivity with 2,4,6-trinitrochlorobenzene (TNCB ) in two AD mouse models: NC/Nga mice and DS-Nh mice. Th1 and Th2 cytokine production of splenocytes was assessed under stimulation with staphylococcal enterotoxin B (SEB) which induces a Th1 response in DS-Nh mice with or without TNCB sensitization. METHODS: We examined clinical skin changes, transepidermal water loss (TEWL), the number of S. aureus on the skin and the serum IgE levels in these mice treated repeatedly with TNCB under conventional conditions (free of fur mites). The splenocytes of DS-Nh mice were cultured with SEB and the cytokine levels in the supernatants were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Significant skin changes were observed on the skin even where TNCB was not applied in both mice treated with TNCB. Increases in S. aureus on the skin and serum IgE levels were detected in DS-Nh mice, but not in NC/Nga mice. In DS-Nh mice, IFN-gamma and IL-13 production of splenocytes increased in the mice treated with TNCB. CONCLUSION: These results suggest that there might be a different mechanism of dermatitis induction between NC/Nga and DS-Nh mice. Th1 responses might play an important role in the development of dermatitis and increase in serum IgE levels in DS-Nh mice through an increase in IL-13 production.     

GATA-3 regulates contact hyperresponsiveness in a murine model of allergic dermatitis

Contact hypersensitivity (CHS) is thought to be associated mainly with the activation of T helper (Th) type 1 cells. However, evidence also suggests that Th type 2 cells (Th2) and cytokines play roles in the development of CHS in humans. The present study examines the Th2 response during the development of CHS in response to 2,4,6-trinitrochlorobenzene (TNCB) in GATA-3-transgenic (GATA-3 Tg) mice. GATA-3 Tg mice were immunized with 7% TNCB applied to abdominal shaved skin. Seven days later, the mice were challenged with 1% TNCB applied to the left ear. Ear swelling, cytokine production in the skin of the ear, and the levels of IgE, IgG1 and IgG2a were measured. Furthermore, we examined the effects of medical treatment on TNCB-induced contact dermatitis using this model. The ear-swelling responses of TNCB-sensitized/challenged GATA-3 Tg mice were significantly greater than those of similarly treated wild-type (WT) mice. The expression of both IL-5 and IL-13 in TNCB sensitized/challenged skin tissues and the IgE response after challenge were obviously increased in the GATA-3 Tg mice, whereas the expression of IFN-γ was identical in the challenged skin tissues of GATA-3-Tg and WT mice. When TNCB-sensitized GATA-3 Tg mice were treated with a high dose of tacrolimus, ear swelling was not significantly decreased, compared with the results in WT mice. These results suggest that GATA-3-induced Th2-dominant responses play a critical role in the pathogenesis of allergic types of dermatitis, such as atopic dermatitis, and may lead to useful new drug development in the future.     

Effects of intranasal mometasone furoate on itchy ear and palate in patients with seasonal allergic rhinitis

BackgroundIntranasal steroids relieve nasal symptoms and ocular itch in allergic rhinitis. Itchy ear and palate are also common and bothersome symptoms but have received little attention in clinical trials of allergic rhinitis.ObjectiveTo ascertain the efficacy of mometasone furoate nasal spray in alleviating itchy ear and palate in seasonal allergic rhinitis.MethodsData were pooled from 4 randomized, double-blind, placebo-controlled trials of mometasone furoate nasal spray, 200 μg/d. Participants rated ear and palate itching from baseline through treatment day 15 as follows: 0, none; 1, mild; 2, moderate; and 3, severe.ResultsA total of 962 study participants received mometasone furoate nasal spray or placebo. Baseline least squares mean itchy ear and palate score was 1.81 for participants receiving mometasone furoate nasal spray (n = 480) and 1.85 for participants receiving placebo (n = 482). Mometasone furoate nasal spray was associated with a greater decrease in itchy and ear palate score vs placebo during the 15-day study period (least squares mean change, ?0.73 vs ?0.45; P < .001). The difference reached significance on day 2 and persisted through day 15 (P ≤ .01 for each day). Results were similar in a subgroup of patients (n = 305) with moderate-to-severe symptoms at baseline. Adverse events with mometasone furoate nasal spray were similar to those observed in other studies of intranasal steroid therapy.ConclusionThese preliminary findings suggest that mometasone furoate nasal spray effectively treats itchy ear and palate in individuals with seasonal allergic rhinitis. Itchy ear and palate is a relevant end point for future clinical trials of allergic rhinitis.     

Skin tape sampling technique identifies proinflammatory cytokines in atopic dermatitis skin

BackgroundMonitoring the effects of biologic therapies in skin diseases will benefit from alternative noninvasive skin sampling techniques to evaluate immune pathways in diseased tissue early and longitudinally.ObjectiveTo establish a minimally invasive profiling of skin cytokines for diagnosis, therapeutic response monitoring, and clinical research in atopic dermatitis (AD) and other skin diseases, particularly in pediatric cohorts.MethodsWe developed a novel method for cytokine profiling in the epidermis using skin tape strips (STSs) in a setting designed to maximize the efficiency of protein extraction from STSs. This method was applied to analyze STS protein extracts from the lesional skin of children having AD (n = 41) and normal, healthy controls (n = 22). A total of 20 cytokines were probed with the ultrasensitive Mesoscale multiplex cytokine assay.ResultsA significant increase in interleukin (IL)-1b (P < .01), IL-18 (P < .001), and IL-8 (P < .001) with a decrease in IL-1a (P < .001) in the stratum corneum of AD lesional skin was found. Concurrently, an increase in markers associated with type 2 inflammatory response was readily detectable in AD lesional skin, including C-C motif chemokine ligand (CCL) 22, CCL 17, and thymic stromal lymphopoietin (TSLP). The levels of IL-1b, IL-18, and TSLP exhibited positive correlations with the AD severity index (Scoring AD index) and skin transepidermal water loss (TEWL), whereas an inverse correlation between IL-1a and Scoring AD index and IL-1a and TEWL was found. The levels of CCL17, CCL22, TSLP, IL-22, and IL-17a correlated with skin TEWL measurements.ConclusionUsing minimally invasive STS analysis, we identified cytokine profiles easily sampled in AD lesional skin. The expression of these markers correlated with disease severity and reflected changes in TEWL in lesional skin. These markers suggest new response assessment targets for AD skin.Trial RegistrationClinicalTrials.gov Identifier: NCT03168113.     

Increased Th2 activity and diminished skin barrier function cooperate in allergic skin inflammation

Atopic dermatitis (AD) is a chronic inflammatory skin disease induced by a complex interaction between susceptibility genes encoding skin barrier components and environmental allergen exposure that results in type 2 cytokine production. Although genetic lesions in either component can be risk factors for disease in patients, whether these pathways interact in the development of AD is not clear. To test this, we mated mice with T‐cell specific expression of constitutively active Stat6 (Stat6VT) that spontaneously develop allergic skin inflammation with Flaky tail (Ft) mice that have mutations in Flg and Tmem79 genes that each affect skin barrier function. Our results demonstrate that over 90% of the Stat6VT transgenic mice carrying the Ft alleles (Stat6VTxFt^?/?) develop severe atopic dermatitis lesions by 3–5 months of age, compared with only 40% of Stat6VT mice that develop disease by 6–7 months of age. Further, histopathological analysis of skin tissues from Stat6VTxFt^?/? mice revealed extensive thickening of the dermis with increased inflammatory infiltrates as compared with Stat6VT mice. Our study suggests that skin barrier defects and altered Th2 responses independently cooperate in the pathogenesis of allergic skin inflammation, similar to effects observed in patients with AD.     

Curcumin inhibits epigen and amphiregulin upregulated by 2,4,6-trinitrochlorobenzene associated with attenuation of skin swelling

Objectives

Contact dermatitis model involving repeated application of hapten is used as a tool to assess dermatitis, as characterized by thickening. Involvement of cell proliferation, elicited by repeated hapten-stimulation, in this swelling has been unclear. Curcumin is reported to reduce inflammation. We examined involvement of cell proliferation and the role of extracellular regulated kinase (ERK) in 2,4,6-trinitrochlorobenzene (TNCB) challenge-induced ear swelling. We also examined the effects of curcumin in this model.

Methods

Mice were sensitized with TNCB to the abdominal skin. Then, they were challenged with TNCB to the ear three times. The ERK activation inhibitor U0126 or curcumin was applied 30 min before each TNCB challenge.

Results

TNCB challenge-induced increased epidermal cell number and dermal thickening. Gene expressions of epithelial mitogen (EPGN), amphiregulin (AREG) and heparin-binding-epidermal growth factor (HB-EGF) were increased in the ears after the last TNCB challenge. Ki-67 immunoreactivity was increased in the dermis in TNCB-challenged ears. TNCB-induced swelling was inhibited by U0126 and curcumin. Curcumin also attenuated TNCB-induced ERK phosphorylation and expression of EPGN and AREG genes.

Conclusion

Ear swelling induced by TNCB challenge might be mediated, in part, by the EPGN- and AREG-ERK proliferation pathway and was inhibited by curcumin.

     

Inhibitory effects of Juglans mandshurica leaf on allergic dermatitis-like skin lesions-induced by 2,4-dinitrochlorobenzene in mice

Allergic dermatitis among common skin diseases is a chronic and recurrent inflammatory skin disorder caused by genetic, environmental, allergens as well as microbial factors. Allergic dermatitis patients clinically present skin erythematous plaques, eruption, elevated serum immunoglobulin E (IgE) and T helper cell type 2 (Th2) cytokine levels. The leaf of walnut tree Juglans mandshurica Maxim (JM) is consumed food and traditional phytomedicine in Asia, China, Siberia and Korea. JM has been reported to have various pharmacological activities, such as anti-tumor, anti-oxidative, and anti-bacterial effects. However, no study of the inhibitory effects of JM on allergic dermatitis has been reported. Here, we demonstrated the effect of JM against 2,4-dinitrochlorobenzene-induced allergic dermatitis-like skin lesions. 0.5% JM or 1% dexamethasone (positive control) applied to the dorsal skin inhibited development of allergic dermatitis-like skin lesions and scratching behavior. Moreover, the Th2-mediated inflammatory cytokines IgE, tumor necrosis factor-α, interleukin (IL)-1, and IL-13, were significantly reduced by JM treatment. Thus JM can inhibit development of allergic dermatitis-like skin lesions in mice by regulating immune mediators, and may be an effective alternative therapy for allergic dermatitis.     

Asthma and allergic diseases are not risk factors for hospitalization in children with coronavirus disease 2019

BackgroundCoronavirus disease 2019 (COVID-19) emerged as a pandemic toward the end of 2019, causing large numbers of people to become infected and die.ObjectiveTo determine whether allergic diseases are a risk factor for hospitalization in COVID-19.MethodsWe conducted a study including 107 pediatric patients after COVID-19 recovery. The International Study of Asthma and Allergies in Childhood Phase 3 questionnaires were distributed together with a detailed history of environmental factors and an allergic evaluation including skin prick tests, specific immunoglobulin E tests, and spirometry. We investigated the prevalence of allergic diseases and evaluated the factors associated with hospitalization in COVID-19.ResultsA total of 61 (57%) patients were hospitalized and 46 (43%) patients were followed closely in the outpatient clinic. The prevalences of allergic rhinitis, asthma, atopic dermatitis, and episodic wheezing were 10.3%, 6,5%, 4.7%, and 3.7%, respectively, within the whole study population. Although having asthma with or without allergic rhinitis, atopic dermatitis, and passive tobacco exposure were not found to be related to hospitalization because of COVID-19, having a pet at home was found to decrease the risk of hospitalization (odds ratio, 0.191; 95% confidence interval, 0.047-0.779; P = .02). Spirometry tests revealed a higher forced expiratory volume in one second to forced vital capacity ratio and a peak expiratory flow reversibility in hospitalized patients than in nonhospitalized ones (P = .02 and P = .003, respectively).ConclusionAsthma and allergic diseases do not seem to be risk factors for hospitalization in children because of COVID-19, and having a pet at home can be a protective effect. Pulmonary function testing seems to be important for monitoring lung damage after COVID-19.     

The role of filaggrin in atopic dermatitis and allergic disease

ObjectiveTo provide an overview of filaggrin biology and the role of filaggrin variants in atopic dermatitis (AD) and allergic disease.Data SourcesWe performed a PubMed literature review consisting mainly of studies relating to filaggrin in the last 5 years.Study SelectionsWe selected articles that were found in PubMed using the search terms filaggrin, atopic dermatitis, skin barrier, and atopy.ResultsFilaggrin plays an important role in the development of AD and allergic disease. Novel methods in measuring filaggrin expression and identifying filaggrin mutations aid in stratifying this patient cohort. We review new insights into understanding the role of filaggrin in AD and allergic disease.ConclusionFilaggrin remains a very important player in the pathogenesis of atopic dermatitis and allergic disease. This review looks at recent studies that aid our understanding of this crucial epidermal protein.     

Effects of tributyltin on the development of atopic dermatitis-like eruptions in DS-Nh mice

BACKGROUND: In the last few decades, numerous chemical compounds have been produced as a result of industrial development. At the same time, the number of atopic dermatitis (AD) patients has been increasing. It has been reported that tributyltin (TBT) compounds have effects not only on the reproductive system but also on the immune system. OBJECTIVE: To investigate whether TBT has an effect on AD, we fed a diet containing TBT to DS-Nh mice, which spontaneously developed dermatitis under conventional conditions. METHODS: DS-Nh mice fed TBT or a control diet were examined for skin changes, number of Staphylococcus aureus on the skin and serum IgE levels. To determine Th1/Th2 cytokine production by lymphocytes, lymphocytes of DS-Nh mice fed TBT and of controls were cultured with staphylococcal enterotoxin B and cytokine levels in the supernatants were measured by ELISA. We observed not only spontaneous dermatitis but also dermatitis induced by sensitization with 2,4,6-trinitrochlorobenzene (TNCB). RESULTS AND CONCLUSION: The AD-like lesions induced by TNCB sensitization were more severe in the mice fed TBT than in those fed the control diet. A greater increase in S. aureus on the skin was observed in the mice fed TBT than in the mice fed the control diet. A decrease in IFN-gamma production and an increase in IL-5 and IL-13 production were observed in the mice fed the TBT diet and treated with TNCB. These findings suggest that the increase in S. aureus and the enhancement of Th2 response induced by TBT exacerbate the AD-like lesions in mice treated with TNCB.     

Clinical and cytologic characteristics of allergic rhinitis in elderly patients

BackgroundThe constant increase in the elderly population worldwide has led to a greater interest in immunologic responses during aging. Thus, special attention to allergic diseases in elderly people has begun to emerge, but little is known about the effect and features of allergic rhinitis in elderly people.ObjectiveTo evaluate the clinical and cytologic characteristics of respiratory allergy and its impact on the quality of life in elderly people.MethodsElderly patients with rhinitis referred to our allergy unit during a 3-month period underwent clinical evaluation and responded to the Rhinasthma Questionnaire. All patients also underwent skin prick testing, measurement of total IgE level, and nasal cytologic analysis. The data were compared with a control group of young adults.ResultsFifty-four patients older than 65 years (mean age, 69.3 years) and 89 young adults (mean age, 26.3 years) with allergic rhinitis were studied. The elderly patients had a less positive family history of atopy (P=.02) and had rhinitis plus conjunctivitis more frequently (P=.002) than young adults, whereas the difference between groups in total IgE level was not statistically significant. On nasal cytologic analysis, the differential count of inflammatory cells did not differ between groups, but in the elderly patients the epithelial-goblet cell ratio was decreased. The quality of life in elderly people was more impaired than in young adults (P=.01).ConclusionIn elderly people with allergic rhinitis, the clinical characteristics are different and quality of life is more heavily impaired compared with young adults.     

Plant chitinase III Ziz m 1 stimulates multiple cytokines, most predominantly interleukin-13, from peripheral blood mononuclear cells of latex-fruit allergic patients

BackgroundIndian jujube is a fruit abundantly cultivated in Taiwan. Its major allergen in latex-fruit syndrome is Ziz m 1 of the chitinase III family. The Ziz m 1 Pichia (rZiz m 1-P) has chitinase activity but not Ziz m 1 E. coli (rZiz m 1-E).ObjectiveThis study examined whether plant chitinase III, using rZiz m 1-P and rZiz m 1-E, can stimulate allergic inflammation similar to that of mammalian chitinases.MethodsFive patients allergic to latex–Indian jujube and five nonallergic controls were evaluated. Their peripheral blood mononuclear cells (PBMC) were cultured with rZiz m 1-E or rZiz m 1-P and pulsed with phorbol 12-myristate 13-acetate. Eleven cytokines were measured by FlowCytomix human Th1/Th2 plex kit and interleukin (IL)-13 by sandwich enzyme-linked immunosorbent assay (ELISA).ResultsInterleukin-13 significantly increased in rZiz m 1-P stimulated PBMC of allergic subjects but was undetectable when stimulated with rZiz m 1-E. The stimulation index significantly increased in IL-13 (380.6 ± 77.33 vs 13.70 ± 6.92), IL-5 (6.70 ± 0.59 vs 0.70 ± 0.37), IL-1β (32.70 ± 0.83 vs 2.10 ± 1.29), and tumor necrosis factor beta (TNF-β) (17.10 ± 2.66 vs 1.50 ± 0.66) between allergic and nonallergic subjects after rZiz m 1-P stimulation. There was no difference in terms of IL-2, IFN-γ, IL-8, and TNF-α production.ConclusionsThe biological function of chitinase activity is required for Ziz m 1 to induce a Th2-specific immune response. This is the first report on PBMC responses of latex-fruit syndrome subjects toward an active exogenous plant class III chitinase that can stimulate multiple cytokines, especially IL-13, from allergic subjects. This implies the role of cross-reactive food allergens in propagating allergic inflammation among allergic subjects.     

Extra domain-A fibronectin is necessary for the development of nasal remodeling in chronic allergen-induced rhinitis

BackgroundExtra domain A–containing fibronectin (EDA-FN) is necessary for the development of allergen-induced lower airway fibrosis. The pathogenesis of fibrosis in allergic rhinitis has not been well studied.ObjectivesTo determine whether EDA-fibronectin is necessary for the development of nasal remodeling in a murine model of chronic allergic rhinitis and in human allergic rhinitis.MethodsEDA(-/-) and wild-type (WT) C57Bl/6 mice were sensitized intraperitoneally and then challenged with inhaled ovalbumin (OVA) or saline for 2 and 5 weeks. Clinical signs of rhinitis and histological analysis of nasal tissue were evaluated. Immunohistological staining for EDA-FN was performed in human tissue of inferior nasal conchae from patients with allergic rhinitis and controls.ResultsAfter 2 weeks of allergen exposure, only goblet cell hyperplasia and perivascular eosinophilia were observed. After 5 weeks, goblet cell number, thickening of the subepithelial layer, and extent and area of collagen deposition were increased in the nasal tissue of WT OVA (ovalbumin)-challenged mice as compared with saline controls (P < .0001, P < .0001, P = .018, and P = .03, respectively). Clinical signs of rhinitis were observed only in WT OVA-challenged mice. In the EDA(-/-) mice exposed to OVA, collagen deposition, collagen area, and subepithelial thickness showed no increase and were similar to saline control mice, whereas goblet cell hyperplasia was similar to WT OVA-challenged mice. EDA-FN expression was prominent in inferior conchae from patients with allergic rhinitis but was absent in control patients.ConclusionEDA-containing fibronectin is necessary for the development of nasal tissue fibrotic remodeling process in both murine and human allergic rhinitis.     

喘可治注射液抑制小鼠变应性接触性皮炎的实验研究

目的：探讨中药喘可治注射液抑制小鼠变应性接触性皮炎（Ⅳ型变态反应）的效果。 方法： 将小鼠按给药不同分为喘可治注射液高、中，低剂量组，地塞米松(DEX)组，苯海拉明及生理盐水组，利用2，4-二硝基氟苯诱发的小鼠左耳变应性接触性皮炎的动物模型，各组于第0 d、1 d致敏前2 h，第2 d和第5 d诱发前2 h及诱发后6 h腹腔注射给药，通过测量左耳厚度差、左耳重量差，体重差及观察左耳病理改变，比较不同剂量喘可治注射液之间以及与对照组之间的疗效。 结果： 喘可治注射液高、中、低剂量和DEX组小鼠左耳厚度及重量的增加，浸润的单核细胞和中性粒细胞的数量均明显低于生理盐水组(P<0.01)；DEX组小鼠左耳红肿的程度虽稍低于喘可治组，但小鼠体重差与其它组比较均有显著差异（P<0.01）；苯海拉明组小鼠变应性接触性皮炎的程度与生理盐水组差异无显著。 结论： 喘可治注射液具有明显抑制小鼠变应性接触性皮炎的作用。     

Toxoplasma gondii Infection Suppresses House Dust Mite Extract-Induced Atopic Dermatitis in NC/Nga Mice

Purpose

Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite that infects humans and animals via congenital or postnatal routes, and it is found worldwide. Modulation of the immune system by parasite infection is proposed to suppress allergic inflammation. Growing evidences have shown that interleukin (IL)-10-producing regulatory B cells (B_regs) and CD4⁺CD25⁺FoxP3⁺ regulatory T cells (T_regs) induced by parasite infection play a critical role in allergic or autoimmune diseases because these cells regulate negatively cellular immune responses and inflammation. Currently, the role of IL-10-producing regulatory B cells in host immune response during T. gondii infection is unknown. In this study, we investigate whether T. gondii infection can suppress the development of unrelated atopic dermatitis (AD)-like lesions.

Methods

AD is a chronically relapsing inflammatory skin disease accompanied by severe itching; for this, we used NC/Nga mice, a well-known experimental model of systemic AD. Repeated exposure to Dermatophagoides farinae crude extract (DfE), known as a major environmental allergen, evokes AD-like skin lesions in NC/Nga mice under specific pathogen-free conditions. NC/Nga mice were intraperitoneally infected with 10 cysts of T. gondii.

Results

T. gondii infection significantly ameliorated AD-like skin lesions in NC/Nga mice. The subpopulation of B_regs and T_regs in the AD mice was expanded in the course of T. gondii infection. In addition, T. gondii infection inhibited Th2 and enhanced Th1 immune response in the DfE-treated AD mice.

Conclusions

We have experimentally demonstrated for the first time that T. gondii infection ameliorated AD-like skin lesions in a mouse model of AD. Our study could in part explain the mechanisms of how parasite infection prevents the development of allergic disorder. Therefore, these immunemechanisms induced by T. gondii infection may be beneficial for the host in terms of reduced risk of allergic immune reactions.     

Exploring Household-level Risk Factors for Self-reported Prevalence of Allergic Diseases Among Low-income Households in Seoul,Korea

Purpose

Indoor risk factors for allergic diseases in low-income households in Korea have been characterized only partially. We evaluated the prevalences of atopic dermatitis, asthma, and allergic rhinitis in Seoul, Korea, to identify key housing and behavioral risk factors of low-income households.

Methods

Statistical analysis of the prevalence of these diseases and various risk factors was conducted using data from a 2010 Ministry of Environment household survey. Logistic regression models were generated using data from 511 low-income household apartments in districts of Seoul.

Results

In general, housing factors such as renovation history (P<0.1) and crowding status (P<0.01) were associated with allergic rhinitis, whereas behavioral factors such as frequency of indoor ventilation (P<0.05) and cleaning (P<0.1) were inversely correlated with atopic dermatitis. Indoor smoking was a major trigger of asthma and atopic dermatitis in low-income households (P<0.05). The presence of mold and water leakage in houses were the most important risk factors for all three diseases (P<0.05).

Conclusions

Various risk factors play a role in triggering allergic diseases among low-income households in Seoul, and health or environmental programs mitigating allergic diseases should be tailored to address appropriate housing or behavioral factors in target populations.     

Epicutaneous sensitization in the development of food allergy: What is the evidence and how can this be prevented?

There is increasing evidence regarding the importance of allergic sensitization through the skin. In this review, we provide an overview of the atopic march and immune mechanism underlying the sensitization and effector phase of food allergy. We present experimental models and human data that support the concept of epicutaneous sensitization and how this forms one half of the dual-allergen exposure hypothesis. We discuss specific important elements in the skin (FLG and other skin barrier gene mutations, Langerhans cells, type 2 innate lymphoid cells, IL-33, TSLP) that have important roles in the development of allergic responses as well as the body of evidence on environmental allergen exposure and how this can sensitize an individual. Given the link between skin barrier impairment, atopic dermatitis, food allergy, allergic asthma, and allergic rhinitis, it is logical that restoring the skin barrier and prevention or treating atopic dermatitis would have beneficial effects on prevention of related allergic diseases, particularly food allergy. We present the experimental and human studies that have evaluated this approach and discuss various factors which may influence the success of these approaches, such as the type of emollient chosen for the intervention, the role of managing skin inflammation, and differences between primary and secondary prevention of atopic dermatitis to achieve the desired outcome.