Project description:Vitiligo is a common autoimmune depigmented dermatology due to the destruction of melanocytes. Much evidence suggests that vitiligo is associated with systemic immune activation. Previous studies have focused on immune cell infiltration in and around lesion areas, while few studies have investigated the cell types and function of circulating immune cells in peripheral blood. We collected peripheral blood from five patients with progressive non-segmental vitiligo (PV) and three healthy controls (HC).Single-cell RNA sequencing(scRNA-seq) is used to investigate the mechanisms of peripheral immune responses in vitiligo patients.
Project description:Vitiligo is a common autoimmune skin disorder. We constructed an induced vitiligo mouse model and performed bulk-RNA sequencing on the skin and 16S rRNA sequencing of feces from vitiligo mice and uninduced mice. Next, we performed skin bulk-RNA sequencing after treatment using ABX. Lastly, we subjected gut microbe-related metabolite hippuric acid to control mice and performed bulk-RNA sequencing on the skin to observe oxidative stress-related gene expression changes.
Project description:Vitiligo is an autoimmune disease that targets melanocytes, and preclinical models of the disease can strongly promote the development of new treatments. This study introduces a vitiligo model using hairless hk14-SCF Tg mice, whose melanocyte distribution closely mimics human skin, enabling comprehensive therapeutic evaluation. Two methods were used to induce vitiligo: (1) hairless hk14-SCF Tg mice received bone marrow-derived dendritic cells (BMDCs) pulsed with the melanocyte-specific peptide gp100 and CD8+ T cells targeting gp100 (PMEL CD8+ T cells), and (2) hk14-SCF Tg mice were crossbred with PMEL TCR transgenic mice without additional treatment. Skin samples were subsequently analyzed using immunohistochemistry, flow cytometry, bulk RNA sequencing, and cytokine assays, confirming that the mechanisms that drive vitiligo in this model closely resemble those of prior mouse models and vitiligo patients. Various treatments— including ultraviolet irradiation, topical corticosteroids, and a JAK inhibitor—were tested and all significantly reduced vitiligo-affected areas, as verified through objective ImageJ analysis. In conclusion, this model addresses key limitations of previous models, offering a robust platform for preclinical treatment evaluation and potentially accelerating clinical translation.
Project description:We performed a comparative immunology case study of client-owned dogs to determine if immune and skin gene expression profiles in spontaneous canine VKH and vitiligo mirror those observed in human autoimmune pigmentary diseases.
Project description:Vitiligo is an acquired depigmentation of the skin inducing a marked alteration of the quality of life of affected individuals. Halting the disease progression and repigmenting the lesional skin represent the two faces of the therapeutic challenge in vitiligo. So far, none of them has been successfully addressed. Oxidative stress and immune system in genetically predisposed individuals participate to the complex pathophysiology of vitiligo. We performed a transcriptome and proteomic analysis on lesional, perilesional and non-depigmented skin of vitiligo patients compared to matched skin controls of healthy subjects. Our results show that the WNT pathway, implicated in melanocytes differentiation, was found to be altered in vitiligo skin. We demonstrated that the oxidative stress decreases WNT expression/activation in keratinocytes and in melanocytes. We developed an ex vivo skin model that remains functional up to 15 days. We then confirmed the decreased activation of the WNT pathway in human skin subjected to oxidative stress. Finally, using pharmacological agents that activate the WNT pathway, we treated the ex vivo depigmented skins from vitiligo patients and successfully induced the differentiation of resident stem cells into pre-melanocytes supporting further exploration of WNT activators to repigment vitiligo lesions. Total of 40 chips. 10 patients (3 biospies per patient: 1 lesional , 1 perilesional and 1 non lesional) ; 10 healthy volunteers (1biopsy in matched anatomical areas)
Project description:We have discovered that human vitiligo patients treated with narrow-band UVB (NBUVB) demonstrated localized resistance to repigmentation in skin sites characterized by distinct cellular and molecular pathways. We used the remaining slides from our immunostaining studies. 1.0 mm2 epidermal scrapes were collected from formalin fixed paraffin embedded (FFPE) transverse sections of biopsies from four paired responding and non-responding vitiligo lesions (8 samples total), following published work (Trejo et al., 2019; Yeakley). The material collected was subjected to whole transcriptome TempO-Seq assay. We used a novel method that combines epidermal scraping and TempO-Seq transcriptome analysis and found that the abnormal environment in non-responding was driven by dysregulated cAMP and WNT/β-catenin signaling pathways. Characterization of abnormal environment that prevents vitiligo repigmentation may open roads for discovery of new drugs that reverse depigmentation.