TO THE EDITOR Hidradenitis suppurativa (HS) is a chronic scarring inflammatory skin disease affecting the pilosebaceous units of the axilla, inframammary folds, groin, and buttocks. Several previous microbiome studies consistently have

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Hidradenitis Suppurativa (HS) is a chronic, scarring, inflammatory skin disease affecting hair follicles in axillae, inguinal, and anogenital regions. Dysbiosis in HS patients compared to healthy subjects is documented. However, whether dysbiosis is specific to particular body sites or skin niches is unknown. We investigated the follicular and skin surface microbiome of the axilla and groin of HS patients (n=11) and healthy individuals (n=10) using 16S rRNA gene sequencing (V3-V4). We sampled non-lesional (HSN) and lesional skin (HSL) of HS patients. β-diversity was significantly decreased (p<0.05) in HSN and HSL skin compared to normal skin with loss of body site and skin niche heterogeneity in HS samples. The relative bacterial abundance of specific microbes was also significantly different between normal and HSN (15 genera) or HSL (21 genera) skin. Smoking and alcohol use influenced the β-diversity (p<0.08) in HS skin. We investigated metabolic profiles of bacterial communities in HS and normal skin using a computational approach.Metabolism, Genetic Information Processing, andEnvironmental Information Processingwere significantly different between normal and HS samples. Altered metabolic pathways associated with dysbiosis of HS skin suggest mechanisms underlying the disease pathology and information about treatment with drugs targeting those pathways.

Fragile X Mental Retardation Protein (FMRP) regulates activity‐dependent RNA localization and local translation to modulate synaptic plasticity throughout the central nervous system. Mutations in the FMR1 gene that hinder or ablate FMRP function cause Fragile X Syndrome (FXS), a disorder associated with sensory processing dysfunction. FXS premutations are associated with increased FMRP expression and neurological impairments including sex dimorphic presentations of chronic pain. In mice, FMRP ablation causes dysregulated dorsal root ganglion (DRG) neuron excitability and synaptic vesicle exocytosis, spinal circuit activity, and decreased translation‐dependent nociceptive sensitization. Activity‐dependent, local translation is a key mechanism for enhancing primary nociceptor excitability that promotes pain in animals and humans. These works indicate that FMRP likely regulates nociception and pain at the level of the primary nociceptor or spinal cord. Therefore, we sought to better understand FMRP expression in the human DRG and spinal cord using immunostaining in organ donor tissues. We find that FMRP is highly expressed in DRG and spinal neuron subsets with substantia gelatinosa exhibiting the most abundant immunoreactivity in spinal synaptic fields. Here, it is expressed in nociceptor axons. FMRP puncta colocalized with Nav1.7 and TRPV1 receptor signals suggesting a pool of axoplasmic FMRP localizes to plasma membrane‐associated loci in these branches. Interestingly, FMRP puncta exhibited notable colocalization with calcitonin gene‐related peptide (CGRP) immunoreactivity selectively in female spinal cord. Our results support a regulatory role for FMRP in human nociceptor axons of the dorsal horn and implicate it in the sex dimorphic actions of CGRP signaling in nociceptive sensitization and chronic pain.

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The cathelicidin antimicrobial peptide LL37 is a critical element in host defense following injury or infection, and its inappropriate expression promotes inflammatory skin diseases such as psoriasis and rosacea. We have shown that cathelicidin promotes inflammation by enabling binding of self-RNA to cell surface scavenger receptors, and that LL37 attaches to scavenger receptors in human psoriatic skin. To examine if this binding is commonly seen in other inflammatory skin diseases, we performed proximity ligation assays (PLA) using antibodies against LL37 and SR-B1, one of scavenger receptors. PLA on human skin demonstrated that the interaction between LL37 and SR-B1 was evident in situ in also rosacea, discoid lupus erythematosus, and chronic pyoderma compared to healthy skin. This result implies that the inflammatory activity of LL37 is mediated by a cell surface, scavenger receptor-dependent interaction in those inflammatory skin diseases, and that the blockade of this interaction is potentially targetable as novel anti-inflammatory therapy. 518Development and characterization of a 3D in vitro model mimicking acneic skin S Bordes, M Laclaverie, P Rouaud-Tinguely, L Marchand and B Closs R&D Department, SILAB, Brive, France Acne is one of the main reason for dermatological consultation since it affects 80% of teenagers and 25% of adults worldwide. It is an inflammatory skin disease of the pilosebaceous unit, involving four essential factors: hyperseborrhea combined to a modification of sebum composition, colonization by Cutibacterium (formerly Propionibacterium) acnes, hyperkeratinization and secreted inflammation. Mimicking these compromised skins is a prerequisite before the development of dedicated therapeutic molecules. Hence, the aim of this study was to develop a new in vitro 3D model mimicking acneic skin, by combining the two main factors involved in the physiopathology: sebum alteration and C. acnes invasion. To do so, normal human keratinocytes were used to generate reconstructed epidermis (RE). During emersion step, RE were either untreated and used as control or treated with: 5.10 4 CFU of C. acnes (CA), in order to mimic the colonization by this opportunistic microorganism: CA RE; peroxidized squalene (PS) in topic during 1 day, in order to mimic the altered sebum composition: PS RE; a combination of C. acnes and peroxidized squalene, in order to mimic acneic skin in a more physiological way: CA-PS RE. For each condition, epidermal characteristics were checked at day 11 (D11) and 14 (D14). As expected, CA-PS RE harbors an increased cytokeratin-5 staining from D11, thus revealing early hyper-keratinization of the model. As evidence of inflammation, supernatant presents higher level of IL8 than CA RE and PS RE. Regarding antimicrobial defenses, expression of specific markers was increased. On the contrary, barrier function was altered, as visualized by lucifer yellow penetration and claudin-1 staining. In conclusion, by combining two main factors involved in the physiopathology of acne, we succeeded ...

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