245 Demodex folliculorum interaction with SARS-CoV2 from a chitin-lipid perspective

Abstract

S | Innate Immunity and Inflammation 240 Serum polyclonal free light chains: possible markers of immune activation in psoriasis R Di Caprio, L Sacchelli, G Di Spigna, M Ricciardone, F Bardazzi, P Ladogana, E Scala, B Covelli, A Balato and L Postiglione 1 Cotugno Hospital, AORN dei Colli, Naples, Italy, 2 Division of Dermatology, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy, 3 Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy, 4 Division of Dermatology and Venereology, Department of Medicine Solna, and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden, 5 Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy and 6 Dermatology Unit, University of Campania “Luigi Vanvitelli”, Naples, Italy The aim of this study was to investigate the role of polyclonal free light chains (FLCs) of the immunoglobulins as markers of immune activation in the management of psoriatic patients on treatment with biologics. The overall study population included 30 patients affected by mild-tosevere psoriasis with either ongoing biological treatment or without any current systemic therapy and 10 healthy controls. FLCs, which include k and l chains, were determined by quantitative nephelometric assay while antinuclear antibodies (ANA) through immunofluorescence. Psoriatic patients showed significant increased levels of k and l FLCs compared to healthy controls. Interestingly, k and l FLCs values were significantly increased only in psoriatic patients with ongoing biological treatment and in particular in responder subjects. Furthermore, correlation of both k and l FLCs with duration of therapy showed significant results. Patients with FLC levels above the normality range and under biological treatment for more than 12 months showed higher odds to be ANA+ respect to patients with FLC levels above the normality range but under biological treatment for less than 12 months. Increased FLCs levels would seem to act as markers of immune reactivation in psoriatic patients on treatment with biologic agents suggesting that the determination of FLCs could have clinical relevance in psoriasis clinical management S190 Journal of Investigative Dermatology (2021), Volume 141 241 Metabolic reprogramming defines myeloid cell function in skin repair 1 1,2,3 S Willenborg and SA Eming 1 Dermatology, University of Cologne, Cologne, Germany, 2 Center for Molecular Medicine Cologne, Cologne, Germany and 3 Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, Cologne, Germany The skin provides a life-sustaining structural and immunological outer barrier of the body and has intrinsic mechanisms that protect the organism from diverse external threats including infections and mechanical injuries. Skin injury induces a complex, dynamic cellular program proceeding in sequential stages of inflammation, tissue growth and differentiation. Cells of the monocytemacrophage lineage are an integral component of an effective repair response. Blood monocytes that are recruited to the side of tissue damage sense a variety of environmental cues of injured tissue and integrate those into a host protective wound healing response. Given that inappropriate macrophage activation underlies a broad range of pathological processes, from chronic inflammatory skin diseases, type 2 diabetes and cancer, macrophages have emerged as an important target to treat disease. The molecular determinants that precisely control the dynamics of macrophage functional plasticity during healing progression are largely unknown and are just beginning to emerge. Previously we have identified phase-specific functions of wound macrophages, ranging from a pro-inflammatory and angiogenic phenotype in the early healing phase towards a type 2-cytokineactivated pro-fibrotic phenotype in the late phase of healing. We aim to understand the functional relationship between cellular metabolism and the execution of specific repair functions in injuryassociated monocytes/macrophages. We will present novel findings showing that different metabolic functions of mitochondria are required to support phasespecific injury-towards-repair programs in wound macrophages. Shaping monocyte/macrophage functions by targeting mitochondria could offer a new approach to pharmaceutically boost regenerative capacity in inflammatory skin diseases. 242 High potency activities of a Tangerine extract to target Rosaceae imprints 2 1 1 1 F Lestienne , H Hernandez-Pigeon , M Galliano , H Delga , S Alvarez-Georges, K André, M Aries, S Bessou-Touya and H Duplan 1 PCO, Pierre FABRE DERMOCOSMETIC, Toulouse, France and 2 Pharmaco-Clinical Research Department, Pierre FABRE Dermo Cosmetic, TOULOUSE, France Rosacea, a chronic skin disorder, is characterized by inflammation and vascular abnormalities of the central facial skin. Cathelicidin LL-37 and VEGF are both specific contributors to physiopathology of Rosaceae and involved in inflammatory and angiogenesis pathways respectively. The aim of this work was to assess the soothing and anti-redness properties of a dermo-cosmetic ingredient in several models exposed to the different components of the rosacea environment. Firstly, the use of human normal keratinocyte primary cell line (NHEK) after a tangerine extract pre-treatment allowed us to show a decrease of VEGF and MMP9 gene expression and IL8 cytokine release after an stimulation by Rosaceae-like cocktail (TLR agonist, LL37, TNFa). In the same way, after a stimulation with Substance P on this previous cell line, an inhibition of the production of cytokines IL-1b and TNFa could be demonstrated. Then, the potency on angiogenesis axis of this compound could be confirmed on a cocultured NHDF/HMVEC based VEGF stimulated Pseudotubes model as well as on the Ca2+ production of a AoSMC model. Moreover, this compound once formulated in a dermo-cosmetic cream was able to inhibit the production of chemokines involved in neurogenic inflammation and EGFR1 pathways in a rosacea reconstructed human epidermis model. These data suggest that a topical Dermo-Cosmetic product with this tangerine extract could be useful to protect against Rosaceae burden in targeting inflammatory and vascular scales. 243 Interim Results of the MANGO Trial: Modified Intermittent Fasting in Psoriasis 1 1 2 2 2 L Grine , NT Hilhorst , N Michels , S Abbeddou , S De Henauw and J Lambert 1 Dermatology, Ghent University Hospital, Ghent, Belgium and 2 Public Health and Primary Care, Ghent University, Ghent, Belgium Modified intermittent fasting (MIF) is associated with metabolic benefits, but its impact on psoriasis has not been explored yet. The MANGO trial investigates how 12 weeks MIF impacts skin, gut and metabolic health in psoriasis patients. Here we report the interim analysis of the crossover trial. A 2-arm pilot crossover randomized controlled trial is being performed. Subjects with mild psoriasis fast twice a week for 12 weeks and monitored another 12 weeks on standard diet. Data is collected on demographics, disease phenotype and activity, diet and exercise, and quality of life. Biochemical parameters in skin, gut and blood are being collected, including microbiotic, inflammatory, permeability and metabolic markers. A total of 24 subjects were enrolled, and one group of 12 participants has fasted for 12 weeks, whereas the other half has continued their regular diet. Fifteen subjects were female, the mean age was 46 years, and the mean Psoriasis Activity Score Index (PASI) was 3.80. In addition to PASI, disease activity was assessed subjectively. Fasting subjects reported improvement more frequently at weeks 6 and 12 (p<0.0001), mentioning less scaling and thickening. Objectively, PASI and Body Surface Area (BSA) did not differ significantly between fasting and regular diet, although both were reduced. Waist circumference and weight were comparable at 6 weeks but significantly reduced in the fasting group at week 12 (p<0,05 and <0,001, respectively). The interim analysis of 12 weeks MIF in psoriasis shows promising results yet remains to be confirmed with the final analysis and with other parameters. Moreover, it would be of great interest to observe which participant profiles were most successful to identify predictive factors. Insights from these data will aid us to understand the complexity of psoriasis and how dietary changes may impact the course of this chronic skin disease. If successful, fasting may be considered as an add-on treatment in psoriasis. 244 Comprehensive Approach to Addressing Skin Inflammaging K Corallo, L Cassereau, D Collins and N Pernodet 1 Research & Development, Estee Lauder Companies, Melville, NY and 2 Darphin Research Laboratories, Paris, France One of skin’s major functions is to serve as a protective barrier to our environment. The skin is exposed to many external aggressors on a daily basis, including but not limited to, various wavelengths of light (UV, blue light, IR, etc.), thermal flux, and pollution (particulates, ozone, etc.). Over the past few decades, environmental exposures have been extensively studied and coined the “exposome.” The skin exposome, which comprises the total daily exposure that our skin endures, can lead to damaging inflammatory cascades within the skin. These inflammatory cascades can be activated by various alarmins such as key inflammatory mediators (e.g. IL-1a) as well as reactive oxygen species (ROS). Alarmins perpetuate a strong inflammatory cascade, which can ultimately result in neutrophil and macrophage recruitment and lead to damaged extracellular matrix structures and appearing, over time, as visible lines, wrinkles, loss of firmness, and sagging. Furthermore, inflammation can induce other visible issues such as redness and hyperpigmentation. While many cosmetic ingredients address phases 1 (initiation) and 2 (activation) of inflamma