Possible role of arginase 1 positive microglia on depressive/anxiety-like behaviors in atopic dermatitis mouse model.

Atopic dermatitis (AD) and mood disorder comorbidities are typical, but the exact mechanism underlying their interplay has not been clarified. In this study, we aimed to identify the possible mechanisms of anxiety/depressive-like behaviors observed in AD, focusing on microglia. AD was induced by Dermatophagoides farinae body extract (Dfb) in NC/Nga mice and anxiety/depressive-like behaviors were analyzed by behavioral assessments such as open field test (OFT), tail suspension test (TST), sucrose preference test (SPT), and social interaction. As clinical symptoms of AD induced, anxiety/depressive-like behaviors were increased in the OFT and TST and serum glucocorticoid was elevated. AD mice showed an increased mRNA expression of interleukin-4 (IL-4) in lymph nodes but decreased arginase 1 (Arg1) mRNA expression without a change of IL-4 in the hippocampus. In addition, AD mice showed microglia with a shortened branch of de-ramified form and astrocytes with longer processes and decreased branching in the hippocampus, especially in the dentate gyrus (DG). The immunofluorescence study of the DG confirmed that Arg1 reduction was associated with microglia, but not astrocytes. Furthermore, glucocorticoid receptor reduction, increased 5-HT1AR, reduced phosphorylated cAMP response element-binding protein (pCREB), and brain-derived neurotrophic factor (BDNF) expression were identified in the hippocampus of AD mice. Notably, an immunofluorescence study confirmed that pCREB was decreased in the DG of AD mice. Collectively, our data suggest that the reduced Arg1 positive microglia might contribute to anxiety/depressive-like behaviors via pCREB/BDNF reduction in AD.

Systemic and local cytokine profile and risk factors for persistent allergic airway inflammation in patients sensitised to house dust mite allergens.

OBJECTIVE: To evaluate cytokine profile, vitamin D status, symptom score and quality of life in patients with persistent allergic airway diseases sensitised to house dust mites (HDM) in comparison with healthy individuals. MATERIAL AND METHODS: Patients sensitized to HDM with persistent AR and having symptoms for at least 2 years with or without AA were involved into the study. Measurements of vitamin D level in serum and IL-10, IL-13, IL-17, IL-22, IL-33 and IFN-gamma in serum and nasal lavage were performed by ELISA. RESULTS: Eighty-one subjects were involved into the study. Serum IL-10 concentration was higher in patients with AR than in patients with AR and AA (6.71 ± 1.73 vs. 1.98 ± 0.24, p < 0.05). IFN-gamma level in nasal lavage was higher in patients with AR and AA than in patients with AR (p < 0.01) and healthy individuals (p < 0.05) (7.50 ± 0.37 vs. 6.80 ± 0.99 vs. 6.50 ± 0.22). Serum IL-22 negatively correlated with IL-22 in nasal lavage, whereas serum IFN-gamma positively correlated with IFN-gamma in nasal lavage. Positive correlation between serum IL-17 and total IgE and negative correlation between IL-17 in nasal lavage and eosinophils in nasal smear were found in patients with AR and AA. Serum IFN-gamma decreased the risk of AR for healthy individuals. Serum IL-10 and vitamin D decreased risk for development of AA for patients with AR. IL-22 in serum and IL-10 and IL-33 in nasal lavage increased this risk. CONCLUSION: Novel cytokines such as IL-22, IL-17 and IL-33 and vitamin D may be involved in pathogenesis of persistent airway inflammation in patients sensitized to HDM.

Airway IL-1ß associates with IL-5 production following dust mite allergen inhalation in humans.

BACKGROUND: Preclinical studies implicate interleukin (IL)-1ß as a key mediator of asthma and have shown the efficacy of IL-1 antagonism for treatment of allergic airway inflammation; human studies in this area are lacking. OBJECTIVES: Our aim was to study the relationship of airway IL-1ß to features of acute allergen-induced asthma exacerbation in humans. METHODS: Dust mite-allergic adults with mild asthma underwent inhalation challenge with Dermatophagoides farinae. Fractional exhaled nitric oxide (FeNO), induced sputum and peripheral blood samples were obtained pre- and 24 h post-challenge. Spirometry was performed before and throughout the challenge at 10-min intervals, and allergen responsiveness was defined by a 20% fall in Forced Expiratory Volume in 1 s (FEV1). Sputum samples were analyzed for inflammatory cells, cytokines and chemokines. Multiple linear regression was employed to test the association between sputum IL-1ß concentration and biomarkers of T helper type 2 (T2)-dominant inflammation. RESULTS: Fourteen volunteers underwent inhaled allergen challenge. Allergen responsive volunteers showed a greater positive change in IL-1ß in sputum following allergen challenge compared to non-responders. Higher pre-challenge sputum IL-1ß was associated with greater increase in sputum IL-5 (p = 0.004), sputum eosinophils (p = 0.001) and blood IL-5 (p = 0.003) following allergen challenge. Allergen-induced sputum IL-1ß production was significantly associated with sputum and blood IL-5 (p < 0.001 and p = 0.007, respectively), sputum IL-4 (p = 0.001), IL-13 (p = 0.026), eosinophils (p = 0.008) and FeNO (p = 0.03). CONCLUSIONS: The positive association between production of IL-1ß and biomarkers of T2 inflammation, particularly IL-5, in humans is consistent with work in animal models that demonstrates a link between IL-1ß and the pathophysiology of allergic asthma. The role of IL-1ß in human asthma warrants further study.

Identification of circular RNA circVPS33A as a modulator in house dust mite-induced injury in human bronchial epithelial cells.

BACKGROUND: House dust mite has been well documented as a major source of allergen in asthma. Circular RNAs (circRNAs) vacuolar protein sorting 33A (circVPS33A, circ_0000455) is overexpressed in a murine asthma model. Herein, we sought to identify its critical action in Dermatophagoides pteronyssinus peptidase 1 (Der p1)-induced dysfunction of BEAS-2B cells. METHODS: The levels of circVPS33A, microRNA (miR)-192-5p, and high-mobility group box 1 (HMGB1) were assessed by quantitative real-time PCR (qRT-PCR) or western blot. Actinomycin D treatment and Ribonuclease R (RNase R) assay were used to characterize circVPS33A. Cell viability, proliferation, apoptosis, migration, and invasion were evaluated by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, and transwell assays, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to quantify interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and IL-6. Direct relationship between miR-192-5p and circVPS33A or HMGB1 was verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assay. RESULTS: CircVPS33A was highly expressed in asthma plasma and Der p1-treated BEAS-2B cells. Knocking down circVPS33A suppressed Der p1-induced injury in BEAS-2B cells. CircVPS33A targeted miR-192-5p. MiR-192-5p directly targeted HMGB1, and miR-192-5p-mediated repression of HMGB1 alleviated Der p1-driven cell injury. Furthermore, circVPS33A modulated HMGB1 expression through miR-192-5p. CONCLUSION: Our findings demonstrated that circVPS33A regulated house dust mite-induced injury in human bronchial epithelial cells at least partially depending on the modulation of the miR-192-5p/HMGB1 axis.

Analysis of the long-term efficacy and safety of subcutaneous immunotherapy for atopic dermatitis.

Introduction: Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease characterized by severe pruritus and eczematous skin lesions. Subcutaneous immunotherapy (SCIT) refers to repeated contact with gradually increasing doses of allergen extracts, which improve patient tolerance to such allergens and controls, or reduces allergic symptoms. This study aimed to explore the long-term efficacy and safety of SCIT for patients with AD sensitized to house-dust mite (HDM). Methods: We conducted a retrospective analysis of 378 patients with HDM-sensitized AD. Among these patients, 164 received SCIT plus pharmacotherapy for 3 years (SCIT group) and the other 214 patients received only pharmacotherapy (non-SCIT group). The scoring atopic dermatitis (SCORAD) and pruritus visual analog scale (VAS) scores, laboratory test results, and adverse effects were recorded. Results: The SCORAD and pruritus VAS scores significantly decreased in the SCIT group. Also, the SCIT group showed higher reduction ratios of SCORAD and pruritus VAS scores than those observed in the non-SCIT group at 3 years after treatment initiation. The risk of development of new sensitization was higher in the non-SCIT group than in the SCIT group (relative risk 1.92 [95% confidence interval {CI}, 1.30-2.85]; p < 0.05). The eosinophil count of the participants significantly differed in the complete response (CR) group (p < 0.05) but not in the non-CR group (p = 0.098). However, the serum total immunoglobulin E value was not significantly reduced (p = 0.204). Of 8421 injections given to the patients, 231 injections (2.74%) showed adverse effects during the treatment period. Conclusion: Three years of SCIT can significantly reduce the severity and pruritus of moderate-to-severe AD with HDM sensitization. Patients who are multisensitized can also benefit from HDM SCIT. Patients can achieve long-term effects, such as prevention of neoallergen sensitization and inhibition of the allergy march.

Avoidance of allergens as an environmental method in the prevention of inhaled allergy symptoms

Asthma and other inhaled allergies are some of the most common paediatric diseases. The association of exposure to allergens with induction and exacerbation of symptoms has been proven. The majority of allergens are permanently or periodically suspended in the air, which leads to impaired quality of life for sensitive patients. Therefore, many methods of prevention and therapy of allergic diseases have been developed. The method of allergen exposure avoidance is often the first and the most significant measure. The present research has been conducted to evaluate, based on scientific data, which measures have the most reliable evidence of effectiveness. Environmental allergen avoidance methods, despite limited evidence supporting their clinical efficacy, are listed as the main therapeutic approaches in most recommendations. The significance of the holistic approach is also emphasised: only simultaneous introduction of several avoidance methods can bring possibly beneficial effects for the patient

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FABP5 as a possible biomarker in atopic march: FABP5-induced Th17 polarization, both in mouse model and human samples.

BACKGROUND: While the incidence of patients with atopic dermatitis (AD) with atopic march (AM) showing respiratory allergy is steadily rising, the pathomechanism is still unknown. There are currently no biomarkers to predict progression of AM. METHODS: To explore the mechanism of AM, patients with AD and AM and healthy controls were recruited and RNA microarray, flow cytometry, quantitative real-time polymerase chain reaction, and immunofluorescence staining were performed. We also co-cultured dendritic cells and CD4+T cells with various Dermatophagoides farinae allergen fractions. Cytokine levels were evaluated using enzyme-linked immunosorbent assay. FINDINGS: Both fatty-acid-binding protein 5 (FABP5) and Th17-related genes were more highly expressed in AM. FABP5 knockdown significantly decreased Th17-inducing cytokines in keratinocytes and IL-17A in T cells from AM patients. Further confirmation was obtained using an AM mice model compared to mice without AM. Der f 1, a major D. farinae allergen, increased FABP5 and IL-17A expression in T cells from AM patients. Higher serum FABP5 levels from AM patients were positively correlated with serum IL-17A levels. INTERPRETATION: FABP5 expression, possibly enhanced by higher epicutaneous and respiratory sensitization to Der f 1, may directly promote Th17 responses in AD patients with AM. Thus, AM progression can be explained by Th17 reaction induced by FABP5. FABP5 was identified as a potential biomarker in AM. FUNDING: This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science and ICT; No. NRF-2017R1A2B4009568), grants of the Korean Health Technology R&D Project, Ministry for Health, Welfare & Family Affairs, and the Republic of Korea (HI13C0010, HI14C1324, HI14C1799).

Association between biomarkers and house dust mite sublingual immunotherapy in allergic asthma.

BACKGROUND: House dust mite (HDM) sublingual immunotherapy (SLIT) has demonstrated efficacy in clinical trials of patients with asthma. Airway inflammation is a characteristic of respiratory allergy, but its relationship to SLIT remains unclear. OBJECTIVE: We evaluate the association between clinical outcomes with pulmonary function and biomarkers in before and after HDM SLIT (UMIN Number 000022390). METHODS: One hundred twelve patients with asthma sensitized to HDM were randomized to add-on 6 standardized quality (SQ)-HDM SLIT to pharmacotherapy or pharmacotherapy alone for 48 weeks. At baseline and end of study, biomarkers, blood eosinophils, serum IgE, serum periostin, fractional exhaled nitric oxide (FeNO), and spirometry and clinical symptoms were measured. Association between biomarkers and an increase in FEV1 of 120 mL or greater were analysed. RESULTS: Sublingual immunotherapy (SLIT) demonstrated a significant reduction of serum periostin (P < .001), FeNO (P < .01), and increase in HDM-specific IgE (P < .05), FEV1 (P < .001) and improvement of clinical symptom scores, when compared to pharmacotherapy. The change in FEV1 correlated with the changes in serum periostin (r = .696, P < .001) and the changes in FeNO (r = .682, P < .001). The independent predictor of improvement in airflow limitation was changed in serum periostin (r2  = .753, P = .013) and FeNO (P = .038). Based on cut-off values derived by receiver operating characteristic analysis (periostin 30.9 ng/mL, FeNO 28.0 ppb), patients were distinguished responders from non-responders, but with no predictive value for blood eosinophils or total IgE. The proportion of patients with both high periostin and FeNO levels was significantly higher in responder than in non-responder (P = .026). CONCLUSIONS AND CLINICAL RELEVANCE: Adding HDM SLIT to pharmacotherapy resulted in reduced serum periostin and FeNO, and improved pulmonary function. Serum periostin and FeNO may be useful biomarkers for prediction of SLIT.

Local allergic rhinitis: nasal allergen provocation testing as a good tool in the differential diagnosis.

Local allergic rhinitis (LAR) is a specific phenotype of allergic rhinitis. One characteristic feature of LAR is a medical history indicative of an allergic disease, negative skin-prick test results, undetectable levels of specific IgE, and a positive allergen-specific nasal provocation test. This paper presents a case of a patient with LAR and underlying house dust mite allergy, who was ultimately diagnosed >10 years after the onset of his first symptoms. Currently, there are only pharmacological treatments available for LAR. However, some studies show encouraging results with the use of allergen-specific immunotherapy in LAR, which offer hope for a future use of this causative treatment in LAR patients. Int J Occup Med Environ Health. 2020;33(2):241-6.

Early-life inhalant allergen exposure, filaggrin genotype, and the development of sensitization from infancy to adolescence.

BACKGROUND: We hypothesized that filaggrin (FLG) loss-of-function mutations modify the effect of allergen exposure on the development of allergic sensitization. OBJECTIVE: We sought to determine whether early-life exposure to inhalant allergens increases the risk of specific sensitization and whether FLG mutations modulate these odds. METHODS: In a population-based birth cohort we measured mite, cat, and dog allergen levels in dust samples collected from homes within the first year of life. Sensitization was assessed at 6 time points between infancy and age 16 years. Genotyping was performed for 6 FLG mutations. RESULTS: In the longitudinal multivariable model (age 1-16 years), we observed a significant interaction between FLG and Fel d 1 exposure on cat sensitization, with the effect of exposure being significantly greater among children with FLG mutations compared with those without (odds ratio, 1.36; 95% CI, 1.02-1.80; P = .035). The increase in risk of mite sensitization with increasing Der p 1 exposure was consistently greater among children with FLG mutations, but the interaction did not reach statistical significance. Different associations were observed for dogs: there was a significant interaction between FLG and dog ownership, but the risk of sensitization to any allergen was significantly lower among children with FLG mutations who were exposed to a dog in infancy (odds ratio, 0.16; 95% CI, 0.03-0.86; P = .03). CONCLUSIONS: FLG loss-of-function mutations modify the relationship between allergen exposure and sensitization, but effects differ at different ages and between different allergens.

The effectiveness of sublingual immunotherapy for house dust mite-induced allergic rhinitis and its co-morbid conditions.

Aim: We investigated sublingual immunotherapy for mite-induced allergic rhinitis and its comorbid allergic conditions. Patients & methods: A prospective case-controlled study of 120 patients (case = 80, control = 40) over 12 months. Results: There was 53.6% reduction in total rhinitis symptom score (p < 0.0001), but not in controls (-7.3%, p = 0.99). The total symptom scores for concurrent asthma decreased from 17.79 to 8.8 (p < 0.0001); for allergic conjunctivitis from 20.89 to 10.0 (p = 0.0002); for atopic dermatitis from 46.40 to 29.38 (p = 0.0004) and 74.6% of patients weaned off nasal topical steroids. The treatment-related adverse reactions were mild and self-limiting. Conclusion: Though sublingual immunotherapy may be more expensive than conventional treatments, it was an adjunctive therapy that improved not only the outcomes for allergic rhinitis, but also its comorbid allergic conditions.

Gardenia jasminoides extract without crocin improved atopic dermatitis-like skin lesions via suppression of Th2-related cytokines in Dfe-induced NC/Nga mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Atopic dermatitis (AD) is a pruritic, chronic, relapsing inflammatory skin disease. Gardenia jasminoides extract (GJE) has been used as a traditional remedy for the treatment of various inflammatory diseases, including AD. The specific effects of the extract components, which include crocin, geniposidic acid, and gardenoside, on inflammatory responses in AD are not entirely clear. AIM OF THE STUDY: We determined the effects of G. jasminoides extract with crocin removed (GJE-C) on AD-like skin lesions in Dermatophagoies farina crude extract (Dfe)-treated NC/Nga mice, a well-known AD mouse model. MATERIALS AND METHODS: To prepare the mice, 150 µl of 4% sodium dodecyl sulfate (SDS) was applied to the shaved dorsal skin or ear of NC/Nga mice 1 h before application of 100 mg Dfe. After 7 d, GJE-C was applied every day for 14 d. We performed behavior, histological, ELISA, assays to evaluate chemokines, cytokines, and skin barrier proteins in skin or serum samples from treated and untreated NC/Nga mice. RESULTS: Topical application of GJE-C improved the severity scores of the AD-like skin lesions, frequency of scratching, and ear swelling in Dfe-treated NC/Nga mice similar to the complete GJE. In addition, GJE-C also reduced serum IgE and chemokine levels as well as the inflammatory response. Topical application of GJE-C also resulted in decreased infiltration of inflammatory cells, such as mast cells, via reduction of Th2 inflammatory mediators, including interleukin (IL)-4, IL-5, and IL-13, pro-inflammatory cytokines, and chemokines, and increased skin barrier protein expression in Dfe-treated NC/Nga mice. The GJE components geniposidic acid and gardenoside inhibited the production of atopic-related chemokines in HaCaT cells, but inclusion of crocin dampened this inhibition of chemokine production. CONCLUSIONS: Together, these findings indicate that GJE-C may improve AD-like lesions by inhibiting the Th2 inflammatory response and expression of chemokines while increasing the expression of skin barrier proteins. These data provide experimental evidence that GJE-C may harbor therapeutic potential for AD.

Domestic mite-induced allergy: Causes, diagnosis, and future prospects.

Allergies to various environmental factors, in particular mite species, represent a considerable healthcare burden with lost productivity resulting from symptoms including asthma, conjunctivitis, rhinitis, and atopic dermatitis. The complexity of mite species and the allergens that they produce complicates diagnosis and treatment; however, the advent of recombinant DNA technologies now allows clinicians to better pinpoint the specific sensitizing agents and creates new opportunities for avoidance or immunotherapy. Here we discuss the advantages and disadvantages of traditional and novel diagnostic and therapeutic platforms, with particular consideration given to multiplex tests able to generate patient-specific allergen profiles. Immunotherapies tailored to such profiles may be safer and more effective than generalized treatments, but many hurdles, including the costs associated with identifying the protein or protein combinations able to exert the safest and most beneficial effects, must be overcome before such therapies can be globally applied.

The Allergen Der p3 from House Dust Mite Stimulates Store-Operated Ca2+ Channels and Mast Cell Migration through PAR4 Receptors.

The house dust mite is the principal source of perennial aeroallergens in man. How these allergens activate innate and adaptive immunity is unclear, and therefore, there are no therapies targeting mite allergens. Here, we show that house dust mite extract activates store-operated Ca2+ channels, a common signaling module in numerous cell types in the lung. Activation of channel pore-forming Orai1 subunits by mite extract requires gating by STIM1 proteins. Although mite extract stimulates both protease-activated receptor type 2 (PAR2) and PAR4 receptors, Ca2+ influx is more tightly coupled to the PAR4 pathway. We identify a major role for the serine protease allergen Der p3 in stimulating Orai1 channels and show that a therapy involving sub-maximal inhibition of both Der p3 and Orai1 channels suppresses mast cell activation to house dust mite. Our results reveal Der p3 as an important aeroallergen that activates Ca2+ channels and suggest a therapeutic strategy for treating mite-induced asthma.

SQ house dust mite sublingual immunotherapy tablet subgroup efficacy and local application site reaction duration.

BACKGROUND: Allergic rhinitis with or without conjunctivitis (AR/C) is common, necessitating evaluation of SQ house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet efficacy in various subgroups. OBJECTIVE: To evaluate 12 SQ-HDM efficacy and safety across subgroups, and the onset, duration, and recurrence of local application site reactions. METHODS: Subgroup (age, sex, race, asthma status, and allergen sensitization) efficacy was assessed using pooled data from 2 previously described trials of daily 12 SQ-HDM vs placebo for AR/C (n = 2,138). Efficacy was measured by average total combined rhinitis score (TCRS; rhinitis daily symptom plus medication score) during the last 8 weeks of treatment. Safety in subgroups and local application site reaction onset, duration, and recurrence were evaluated using pooled data from 5 previously described trials of SQ HDM SLIT-tablet (n = 2,923). RESULTS: Significant (based on 95% confidence intervals [CIs]) reduction in TCRS was seen with 12 SQ-HDM relative to placebo across all subgroups, with TCRS improvements ranging from 15% to 25%. The AE profile was generally similar within subgroups. Approximately 95% of local application site reactions were mild to moderate in severity. Median duration on day 1 of treatment for the most common local application site reactions (throat irritation, oral pruritus, ear pruritus, and lip swelling) ranged from 30 to 60 minutes; median first day of onset ranged from days 1 to 4 of treatment; median days that reactions recurred ranged from 3 to 12 days. CONCLUSION: Treatment with 12 SQ-HDM consistently improved symptoms and was well tolerated in relevant subgroups of subjects with HDM AR/C. Local application site reactions to 12 SQ-HDM were typically mild to moderate and transient.

A Three-Year Course of House Dust Mite Sublingual Immunotherapy Appears Effective in Controlling the Symptoms of Allergic Rhinitis.

Background Allergic rhinitis is the most common allergic disorder. Although the management of the disease is successful in many patients, based on guidelines, some of them remain with symptoms uncontrolled with pharmacotherapy. Presently, there is no substantiated information on the control of allergic rhinitis in patients who underwent sublingual immunotherapy. Objective The purpose of this prospective follow-up study was to assess the control of allergic rhinitis in adults after a three-year course of house dust mite sublingual immunotherapy. Methods This prospective real-life study was designed to include adults with moderate to severe allergic rhinitis sensitized to house dust mite who underwent a three-year course of sublingual immunotherapy. Control of symptoms was assessed by Rhinitis Control Assessment Test (RCAT) after three years of house dust mite sublingual immunotherapy. Additionally, patients assessed their symptoms by utilizing a visual analog scale. Results A total number of 86 consecutively enrolled patients (46 (53.49%) men; mean age 26.10 years (SD = 5.85)) with moderate to severe allergic rhinitis and clinically relevant sensitization to house dust mite were evaluated. When assessed by RCAT on the third year, 74 (86.05%) had well-controlled symptoms and 20 (27.03%) of them were completely controlled. A significant reduction in visual analog scale scores-from 7.52 cm at baseline to 2.31 cm-was established ( P < 0.0001). There was a strong negative correlation between RCAT scores and visual analog scale (r = -0.65; P < 0.01). Conclusion This study provided evidence that a three-year course of house dust mite sublingual immunotherapy appears effective in controlling the symptoms of allergic rhinitis.

LIGHT-HVEM signaling in keratinocytes controls development of dermatitis.

Dermatitis is often associated with an allergic reaction characterized by excessive type 2 responses leading to epidermal acanthosis, hyperkeratosis, and dermal inflammation. Although factors like IL-4, IL-13, and thymic stromal lymphopoietin (TSLP) are thought to be instrumental for the development of this type of skin disorder, other cytokines may be critical. Here, we show that the tumor necrosis factor (TNF) superfamily protein LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for binding to HVEM, a receptor expressed on T lymphocytes) is required for experimental atopic dermatitis, and LIGHT directly controls keratinocyte hyperplasia, and production of periostin, a matricellular protein that contributes to the clinical features of atopic dermatitis as well as other skin diseases such as scleroderma. Mice with a conditional deletion of the LIGHT receptor HVEM (herpesvirus entry mediator) in keratinocytes phenocopied LIGHT-deficient mice in exhibiting reduced epidermal thickening and dermal collagen deposition in a model of atopic dermatitis driven by house dust mite allergen. LIGHT signaling through HVEM in human epidermal keratinocytes directly induced proliferation and periostin expression, and both keratinocyte-specific deletion of HVEM or antibody blocking of LIGHT-HVEM interactions after disease onset prevented expression of periostin and limited atopic dermatitis symptoms. Developing reagents that neutralize LIGHT-HVEM signaling might be useful for therapeutic intervention in skin diseases where periostin is a central feature.