Project description:Atopic dermatitis (AD) is the most common chronic inflammatory skin disorder, characterized by intense itch and recurrent eczematous lesions. Due to lack of proper therapy, the strategies of T cell modulators in combination with targeting keratinocytes and/or myeloid cells might hold promise for achieving disease control in AD patients better than T cell modulators alone. we used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during HY209 treatment in mouse skin
Project description:Background: Chemical-induced sensitization is a major health concern. To date, no internationally accepted method is able to discriminate a skin from a respiratory sensitizer. The identification of an immune profile specific to skin or respiratory sensitizersation is therefore scientifically relevant. Methods: Female BALB/c mice were dermally exposed to a skin- (dinitrochlorobenzene, DNCB), or to a respiratory sensitizer (phthalic anhydride, PA) at day 0 (D0) and D5 to initiate allergic sensitization and at D10, D11 and D12 to induce elicitation. Auricular lymph nodes (LN) were collected at D0, D3, D7, D10 and D13. Single cell transcriptomic analyses were performed in order to identify immune cells proportions and markers expression. Results: Exposure to both sensitizers induced a strong immune reaction demonstrated by an increase of mature B cells and an evolution of the T cell subpopulations, with an increase of follicular and memory T cells. The proportion of NKT, Th2 and Th9 cells and the levels of IgE increased specifically during PA exposure. Follicular, memory and helper T cells showed distinct transcriptomic responses to DNCB or PA. The proportion of dendritic cells strongly increased starting from D10 in mice exposed to DNCB and those cells showed a specific genetic signature towards the skin sensitizer. Conclusion: A distinct transcriptomic signature was identified in immune cells during sensitization to DNCB or PA in this study.
Project description:Female C57BL/6J mice, 8 weeks old, were DNCB-induced dermatitis on skin. For the effect of tonsil-derived mesenchymal stem cells (T-MSCs)treatment, cells were added to dermatitis model. After 10 days, spleen cells were isolated for RNA expression analysis.
Project description:Inflammation and autoimmunity are known as central processes in many skin diseases, including psoriasis. It is therefore important to develop pre-clinical models that describe disease-related aspects to enable testing of pharmaceutical drug candidates and formulations to essentially develop safe and effective treatments. A widely accepted pre-clinical model of psoriasis is the imiquimod (IMQ)-induced skin inflammation mouse model. It is primarily used to assess safety and efficacy of drug candidates for treatment of psoriasis but can also be used to evaluate the performance of drug delivery systems. In this model, topically applied IMQ provokes local skin inflammation, which is characterized by elevated levels of cytokines and chemokines, cellular infiltration, and increased epidermal thickness. In this study, we investigated the abundance of a subset of matrix metalloproteinases (MMPs) in skin from mice with IMQ-induced skin inflammation and skin from naïve mice using targeted proteomics. Our findings revealed a significant increase in the abundance of MMP-2, MMP-7, MMP-8, and MMP-13 after treatment with IMQ compared to the control skin, while MMP-3, MMP-9, and MMP-10 were exclusively detected in the IMQ-treated skin. The increased abundance and broader representation of MMPs in the IMQ-treated skin provide valuable insight into the pathophysiology of skin inflammation in the IMQ model. Specifically, the changes in the MMP profiles observed in the IMQ-treated skin resemble the MMP patterns found in skin lesions of individuals with psoriasis. Ultimately, the differences in MMP abundance under IMQ-induced inflammation as compared to non-inflamed control skin can be exploited as a model to investigate drug efficacy or performance of drug delivery systems.
Project description:To assess the preclinical Aldara model, the proteomic response of mouse skin to topical applied Aldara cream was assessed using untargeted LC-MS. Skin from sham treated or treated with the Aldara cream were compared for 4 independent experiments after 8 days of treatment.