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Reflectance confocal microscopy (RCM) is a non-invasive imaging technology that allows real-time examination of the skin at nearly histologic resolution. It has been proved to be valuable in the clinics, but its application in animal models is limited. The main objectives were to identify characteristic confocal features in healthy murine skin, and evaluate the cutaneous alterations in the mouse model of oxazolone-induced dermatitis. A VivaScope® microscope was used to take horizontal optical sections of the skin from the stratum corneum to the dermis, up to the maximum optical depth of 250 μm.
Type 2 immunity is a major driver of inflammatory allergic skin disease. However, the fundamental role of type 2 immunity in the context of skin homeostasis and its influence on skin tissue function is not well understood. Here we show that type 2 innate lymphoid cells (ILC2s) are the predominant skin tissue-resident immune cells that secrete type 2 cytokines in homeostasis. ILC2s in the skin have a distinct subset of activating signals when compared to tissue resident ILC2s from other tissues. The activation of ILC2s and secretion of IL-13 is coupled to the stage of the hair follicle cycle.
Differentiating psoriasis from eczema can be challenging for lesions presenting with atypical phenotype, minimal/chronic inflammation or in distinct anatomical locations (scalp, auricular, palmoplantar and flexural areas). Unlike skin biopsies, tape stripping is a non-invasive sampling technique. We aimed to further develop this tool to facilitate the diagnosis of psoriasis and eczema and identify a simple but robust non-invasive diagnostic algorithm. Tape samples have been collected from psoriatic (n=35) and eczematous (n=21) skin and of healthy controls (n=23), followed by protein extraction and peptide identification using liquid chromatography tandem mass-spectrometry (LC-MS-MS), with data analysis in MaxQuant and Perseus softwares.
The goal of this study was to predict clinical response to methotrexate (MTX) in atopic dermatitis patients, based on clinical characteristics and serum biomarkers We retrospectively included 78 AD patients treated with MTX in daily practice. Patients were classified as responders to MTX treatment if they achieved an Investigators’ Global Assessment of 0-2 without the use of oral corticosteroids after 6 months of treatment. Clinical characteristics were extracted from the electronic patients file.
Rosacea is a common inflammatory skin disorder characterised by recurrent flare-ups and neoangiogenesis, eventually culminating in persistent erythema. Cathelicidin antimicrobial peptides and their upstream activating protease Kallikrein 5 (KLK5) have been implicated in rosacea, yet the pathogenic mechanisms that lead to flare-ups remain elusive. In gene expression analyses, we find selective overexpression of type I interferon (IFN) specifically during acute flare-ups of disease. Using an established in vivo model of rosacea, we find that IFN expression in situ, critically dependent on plasmacytoid dendritic cells (pDCs), drives a predominant TH17/22 profile, similar to the signature found in our patient cohort.
The aim of this study was to investigate the therapeutic and immunomodulatory properties of P28GST in an experimental model of psoriasis. The potent anti-inflammatory and immunomodulatory properties of P28GST, a protein-derived from the schistosome helminth parasite, have been previously demonstrated in experimental colitis by our group and have recently led to a phase 2 clinical trial in Crohn’s disease patients. The therapeutic potential of P28GST was investigated in the murine model of psoriasis induced by daily application of Imiquimod during 5 days.
Sweet Syndrome (SS) is characterized by an accumulation of mature polymorphonuclear cells (PMN) in the skin. Ten percent of SS patients have an associated myeloid neoplasm (MN) but the pathophysiological link between these two diseases is unclear. To have a better insight in skin-infiltrating PMN clonality of MN-associated SS, we conducted a retrospective study and reviewed patients with concomitant SS and MN diagnosed at Saint-Louis or Saint-Antoine hospital, Paris, France, between 2010 and 2018.
Tylosis with Oesophageal Cancer (TOC) is a rare autosomal dominant syndrome characterised by palmoplantar keratoderma and a high lifetime risk of oesophageal squamous cell carcinoma. TOC is associated with gain-of-function mutations in RHBDF2, encoding iRhom2, which regulates the stress-responsive keratin cytoskeleton and the maturation of ADAM17; a major sheddase of several pro-inflammatory cytokines. Thus, we hypothesised that TOC tissue is associated with an aberrant inflammatory milieu. Initially, we performed RNAseq on normal and TOC oesophagus tissue and following analysis with CIBERSORT and xCell, we identified elevated numbers of mast cells and M2 macrophages in TOC biopsies, which is indicative of a type 2 immune response.
Epidermal growth factor receptor inhibitors (EGFRi) and mitogen activated protein kinase inhibitors (MEKi) are commonly used in oncology. They are associated with adverse cutaneous reactions in 80% of patients. These reactions can be divided into on-target pharmacodynamic effects, specifically inhibition of keratinocyte cell proliferation, and pro-inflammatory effects which culminate in a sterile folliculitis. EGFRi and MEKi are known to inhibit an immune checkpoint inhibitor, Programme Death Ligand 1 (PD-L1), whose down-regulation might contribute to this inflammatory reaction.
Aryl hydrocarbon receptor (AhR) is an environmental sensor for immune responses. In skin, AhR is expressed in several cells, including keratinocytes and Langerhans cells (LC). The current evidence of how AhR would activate or inhibit skin immune responses is controversial, likely due to the different functional role of AhR in different cells and different haptens or peptides used. We crossbred langerin-Cre with AhR-loxP to address the role of AhR in langerin-expressing cells using epicutaneous ovalbumin sensitization.
A20 is a known key regulator of NF-κB activity and inflammatory responses. A20 plays a role also in the control of cell death and cell death receptor signaling. Although A20 is widely accepted as an anti-apoptotic protein, we demonstrate that elevated expression of A20 in both human and murine keratinocytes results in sensitisation to TNF-induced cell death. We prove that Ripoptosome formation in A20 overexpressing cells is a prerequisite for TNF-induced cell death execution. We demonstrate that both canonical and non-canonical NF-κB signaling pathways are regulated upon increase of A20 expression.
Demodex mites are normal residents of the pilosebaceous follicles of healthy human facial skin, at low density, without inducing inflammatory response by skin resident cells (SRCs). When the Demodex population increases, such as in rosacea, an inflammatory response is initiated. The aim of this study is to evaluate how Demodex mites modulate inflammation in SRCs. Skin biopsies from rosacea patients were assessed histologically. Hair follicles were dilated or ruptured, contained mites and occasional inflammatory cells.
This study aimed to construct a predictive serum biomarker signature, measured on a single time point, that can be used for the early identification of difficult-to-treat atopic dermatitis (AD) patients requiring treatment with systemic immunosuppressive drugs. We retrospectively included 74 severe AD patients (EASI >21 before start of treatment) who could be controlled with topical steroids (“controlled disease”) and 78 severe AD patients (EASI >21 before start of treatment) eventually requiring treatment with systemic immunosuppressive drugs (“difficult-to-treat”).
The goal of this study was to investigate the effect of anti-interleukin(IL)-4 and IL-13 treatment with dupilumab on the peripheral blood T cell compartment in moderate to severe atopic dermatitis patients. In a pilot study including six AD patients, peripheral blood mononuclear cells were isolated before and after 4 and 16 weeks of dupilumab treatment. In a validation study including twelve AD patients, PBMCs were isolated before and after 4, 16 and 52 weeks of dupilumab treatment. T cell skewing based on cytokine expression, including the cytokines IL-4, IL-13, IL-17A, IL-22 and interferon gamma (IFNg), within the total and skin-homing (CLA+, CCR4+, CCR10+) CD4+ T cell population was analyzed using flow cytometry.
The aim of the present study was to quantify the biological effects of a Pickering emulsion co-encapsulating an immunosuppressant drug [ciclosporin A (CsA) or tacrolimus (Tac)] in biodegradable and biocompatible PLGA nanoparticles (NP), together with Calcitriol into the dispersed oily phase on both respective cell targets, immune T cells and keratinocytes, in vitro, as well as skin explants. PBMC freshly isolated from blood of healthy volunteers were assessed for IL-2 production by ELISA, and for proliferation and activation under CD3*CD28 activation for 6 days as measured by CFSE staining and membrane antigen expression, respectively, using flow cytometry.
The goal of this study was to show the biological heterogeneity of adult AD based on serum biomarkers and to study the heterogeneity of paediatric AD by identifying biomarker profiles in children within different age groups and compare these profiles with adult biomarker profiles, as an indication of persistence of disease. A cohort of 152 moderate to severe adult AD patients and a cohort of 240 mild to severe paediatric AD patients (aged 0-17 years) were included in this study. 143 serum analytes were measured on a multiplex immunoassay platform in both cohorts.
Many studies have examined the effects of particulate matter (PM) on skin damage and its underlying anthropogenic effects. Air pollution containing PM had been found to increase the incidence of inflammatory skin diseases, extrinsic aging. Exposure to PM induces inflammatory cytokine production and reactive oxygen species (ROS). Among the components of air pollution, substances with a size of PM 2.5 were reported to be absorbed through the pores of the skin. Titanium dioxide(TiO2) can be used in models of nanopariticles.
Increased evidence suggests that alterations in chromatin structure result in aberrant pro-inflammatory cytokines expression that leads to prolonged inflammatory responses. CCCTC-binding factor (CTCF) is a transcriptional repressor that insulates the expression of neighbouring genes and is involved in chromatin interactions between distal and proximal gene regulatory elements. However, the role of CTCF in the control of pro-inflammatory cytokines expression in the skin cells remains unknown. Here, we show that CTCF is expressed in the nuclei of normal human epidermal keratinocytes (NHEK) and dermal fibroblasts (DF), while its siRNA-mediated deficiency induces cell-type specific changes in pro-inflammatory gene expression.
The skin serves an important role in the defense mechanism against pathogens and possesses immunomodulatory functions. Several in vitro models that mimic different aspects of local skin inflammation exists. The use of ex vivo human skin organ culture had been reported previously. However, comprehensive data of the cytokine secretory profile of the system and kinetics have not been reported. The aim of the current study was to investigate the levels of key cytokines secretion upon lipopolysaccharide (LPS) stimuli.
Investigation of interleukin (IL)-26 in hidradenitis suppurativa (HS), through its involvement in the antimicrobial activity. IL-26 was assessed in HS patients through gene expression and protein analysis at skin and circulating levels. Ex vivo HS organ skin cultures, together with IL-26 antibody treatment, were performed to determine IL-26 activity. HS and healthy control (HC) PBMC were even or no silenced with IL-26 siRNA in order to measure antimicrobial, cytotoxic and phagocytic activities against S.