892 Atopic dermatitis endotypes based on allergen sensitization, staphylococcus reactivity, and underlying systemic inflammation A Leonard 1 , J Wang 2 , LYu 2 , YD Estrada 1 , L Greenlees 2 , R McPhee 2 , A Ruzin 2 , E Guttman- Yassky 1 and M Howell 2 1 Mount Sinai, New York, NY and 2 MedImmune, LLC, Gaithers- burg, MD Atopic dermatitis (AD) is a chronic inflammatory disease with significant local and systemic inflammation and barrier disruption. AD is associated with increased risk of allergen sensi- tization and skin colonization by Staphylococcus aureus. The heterogeneity of AD is un- known, and its complexity suggests its subdivision into several endotypes. We performed proteomic profiling of allergen sensitivity, antibody levels to S. aureus antigens, and circu- lating inflammatory mediators to characterize AD subsets in 76 subjects with moderate-to- severe AD and 39 healthy controls. We tested sera for total serum IgE levels and allergen- specific IgE using a panel of 119 allergens. We analyzed sera for anti-S. aureus antigen- specific IgE and IgG antibodies and profiled sera for more than 1300 proteins by SOMAscanÒ to detect differential expression of inflammatory mediators. Total serum IgE levels were significantly (p<0.001) elevated in subjects with AD vs. controls. AD subjects exhibited greater reactivity to environmental and food allergens vs. controls. Separation of AD subjects by allergen sensitization corresponded with differential IgE and IgG antibody levels against S. aureus antigens. Sensitization of AD subjects with perennial or seasonal allergens corre- sponded with higher anti-Toxic Shock Syndrome Toxin-1 IgE antibody levels, while sensiti- zation to food allergens in AD corresponded with higher IgG antibody levels against alpha and delta toxins and clumping factors A and B. Segmentation based on allergen sensitization corresponded with significant differences in circulating inflammatory mediators, suggesting inherent variances in AD endotypes. Overall, this study presents potential subsets of AD, which exhibit unique systemic inflammation patterns despite similar cutaneous presentations. Further characterization of AD endotypes will aid in selecting more targeted therapy in AD. 893 Skin remodeling after probiotic stimuli L Vasquez-Pinto 1 , D Rodriguez 2 , D Zimbardi 1 , J Nicoli 3 and F Martins 3 1 Advanced Cosmetic Technologies, Cajamar, Sao Paulo, Brazil, 2 Microbiology, Cajamar, Sao Paulo, Brazil and 3 Microbiology, Belo Horizonte, Minas Gerais, Brazil Skin microbiome has an important role as host guardian, contributing to several physiological functions including skin turnover and expression regulation of several extracellular matrix proteins that contribute to the youth appearance of skin. It is postulated that skin microbiome communicates with skin cells regulating protein turnover and tissue remodeling. Probiotics are widely used for improving the health of digestive tract that reflects itself on skin surface. Topical use formulations containing probiotic technologies are usually addressed to reduce skin sensitivity. Little is known about the mechanisms trigged by probiotics that modulates skin turnover and extracellular matrix proteins synthesis. In this study, we tested different probiotic technologies in a 3D model and showed that these technologies are able to modulate significantly gene and protein expression related to skin maintenance and remodeling, differently modifying skin milieu depending on the technology used. This remodeling is important to maintain skin correct responsiveness to external stimulus and stimulate extracellular matrix proteins that sustain skin shape and volume. Altogether our results suggest that probiotics and the microbiome are important to maintain skin health and that these technologies can be addressed to preserve skin integrity. 894 Poly(I:C) and GAG inhibit exogenous HSV1 infection in the barrier dysfunctional 3D epidermal model E Sato 1 , K Hiromatsu 1 , K Murata 2 and S Imafuku 3 1 Department of Microbiology and Immunology, Fukuoka University, Fukuoka, Japan, 2 The Center for Electron Microscopy, Fukuoka University, Fukuoka, Japan and 3 Dermatology, Fukuoka University, Fukuoka, Japan Skin barrier dysfunction often induces severe herpes simplex virus (HSV) infection that is known as Kaposi’s varicelliform eruption (KVE). KVE often occurs on patients with atopic dermatitis or genetic skin disease such as Dariers disease (DD). The mechanism of KVE has not been clearly proved, and the preventive methods have not been found. We previously established a skin barrier dysfunctional 3D model using siRNA of ATP2A2 of which gene mutation is confirmed in DD. This 3D model has dyskeratosis and TEM observation clearly revealed epidermal cleft that is caused by the absence of desmosome at intercellular space in ATP2A2 silenced-3D (DD-like) epidermis. We applied 510 5 PFU of HSV1 on the stratum corneum and then confirmed that HSV1 could not invade into the deep epidermal layers in the normal 3D model as previously reported. However, silencing of ATP2A2 induced HSV1 invasion from granular to basal layer at 24 h after infection confirmed by immunofluores- cence of HSV1-gB and qPCR of gD. Unexpectedly, the expression of IFNB1 or ISG15 in the DD-like epidermis was downregulated compared with control although there was no sig- nificant difference in the normal 2D-culture system. Application of Poly(I:C) or Poly(I:C)/LL37 complex upregulated IFNB1 expression in the DD-like epidermis at 3h after stimulation and pretreatment of Poly(I:C) or Poly(I:C)/LL37 significantly suppressed gD and VP16 gene expression at 24h after infection. Next, for compensating epidermal barrier dysfunction, we pretreated the epidermis with white petrolatum (WP) plus glycosaminoglycans (GAG) on the DD-like epidermis. Topical application of WP or WP/heparin revealed GAG ointment strongly suppresses HSV1 infection. Our results suggest that this barrier dysfunctional model well reproduces the exogenous HSV1 infection, and it may be useful for discovery of new prophylaxis for KVE. 895 Trichomonas vaginalis exosomes deliver cargo to host cells and mediate host: Parasite interactions O Twu 1 , N de Miguel 2 , G Lustig 3 , G Stevens 4 , A Vashishit 5 , J Wohlschlegel 6 and P Johnson 7 1 Dept of Dermatology, University of California - San Francisco, San Francisco, CA, 2 Labo- ratorio de Para´sitos Anaerobios Instituto de Investigaciones Biotecnolo´gicas-Instituto Tec- nolo´gico Chascomu´s (IIB-INTECH), Buenos Aires, Argentina, 3 Africa Health Research Institute, Durban, South Africa, 4 UCLA, Los Angeles, CA, 5 The Genomics Institute of the Novartis Research Foundation, San Diego, CA, 6 Biological Chemistry, UCLA, Los Angeles, CA and 7 Microbiology, Immunology & Molecular Genetics, UCLA, Los Angeles, CA Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogential tract where it remains extracellular and adheres to vaginal, urethral or prostate epithelial cells. Infections range from asymptomatic to highly inflammatory, depending on the host immune system and the parasite strain. We have found that T.vaginalis produces and secretes microvesicles with physical and biochemical properties similar to mammalian exosomes. The parasite-derived exosomes are characterized by the presence of RNA and core, conserved exosomal proteins as well as parasite-strain-specific proteins. We demon- strate that T.vaginalis exosomes fuse with and deliver their contents to host cells and modulate host cell immune responses. Moreover, exosomes from highly adherent parasite strains increase the adherence of poorly adherent parasites to vaginal and prostate epithelial cells. In contrast, exosomes from poorly adherent strains had no measurable effect on parasite adherence. Additionally, exosomes from parasite strains that preferentially bind prostate cells increased binding of parasites to these cells relative to vaginal cells. Our research establishes that parasite exosomes act to modulate host:parasite interactions, and reveal a potential role for exosomes in promoting both parasite:parasite communication and host cell colonization. Future studies of interactions between pathogen and/or commensal microbes exosomes and human epithelium may reveal additional insights into factors that can promote or inhibit host immunity. 896 MiR-137 induced by hyperglycemia inhibits REG3A expression to delay wound healing in diabetes Y Lai East China Normal University, Shanghai, China Impaired expression of the antimicrobial protein REG3A /RegIIIg has been shown to delay wound healing in diabetes, but the underlying mechanism is not completely explored. Here we show that hyperglycemia induces miR-137 to inhibit REG3A expression in keratinocytes. Mechanistically, the expression of miR-137 was induced by high glucose via the activation of p53 at Ser 20 in keratinocytes. Consistently, the expression of miR-137 was significantly increased in skin wounds of diabetic mice compared to that in normal mice. Increased miR- 137 directly targeted the 3’UTR3 untranslated regions) of REG3A to decrease the stability of REG3A mRNA and then decreased REG3A protein, thus inhibiting keratinocyte proliferation but increasing the production of pro-inflammatory cytokines to delay wound healing in diabetes. The inhibitory effect of miR-137 was further confirmed in vivo as the administration of miR-137 antagomir into mouse skin abrogated the inhibitory effect of hyperglycemia on REG3A and promoted wound healing in diabetic mice. Taken together, these observations demonstrate that hyperglycemia inhibits REG3A via the induction of miR-137, and suggest that local modulation of miR-137 might be a potential therapeutic strategy for management of wound healing in diabetes. 897 A high fat and high sugar diet (Western diet) predisposes mice to imiquimod- induced psoriasiform dermatitis S Yu 1 , X Wu 1 , Y Zhou 2 , D Han 2 and ST Hwang 1 1 Department of Dermatology, UC Davis School of Medicine, Sacramento, CA and 2 Department of Dermatology, University of California Davis School of Medicine, Sacramento, CA A growing body of epidemiological research has clearly shown that obesity is often co- associated with psoriasis. A high fat and high sugar diet (i.e., Western diet, WD) that char- acterizes the diet in many Western countries plays a role in the development of obesity. In the current study, we hypothesize that WD predisposes mice to psoriasiform dermatitis (PsD) that resembles human psoriasis and examine expression of psoriasis-related cytokines in WD- and control chow-fed mice. Herein, C57BL/6 mice were fed with WD or control diet (CD) for up to 16 weeks. Imiquimod (IMQ) cream (5%) or vehicle cream was then applied to both ears of each mice for 5 consecutive days (from day 0 to day 4) to induce PsD. Ear thickness was measured daily (day 0 to day 5). After euthanizing mice on day 5, ear tissues were harvested for RT-PCR. For mice fed for 8 weeks and 12 weeks, ear thickness change at day 5 showed no statistically significant difference between WD and CD groups though WD mice tended to have more prominent ear swelling (week 12: 0.2300.045mm vs. 0.1400.044mm, p¼0.138). After 16 weeks, however, IMQ induced significantly more ear swelling in WD mice than CD mice on day 5 (0.2440.033mm vs. 0.1410.040mm, p¼0.010). RT-PCR revealed, after feeding for 16 weeks, baseline expression levels of IL-17A and IL-22 were 30- fold (p¼0.045) and 20-fold (p¼0.016) higher, respectively, in WD group as compared with CD group while expression of IL-23, TNF-a, and IL-6 showed no significant difference. Based on these results, we propose that WD potentiates PsD by increasing expression of IL-17A and IL-22. In humans, weight reduction may be beneficial in reducing psoriatic risk and/or increasing the efficacy of psoriatic treatment. ABSTRACTS | Innate Immunity, Microbiology, Inflammation S152 Journal of Investigative Dermatology (2018), Volume 138