PhD defence (in french) Titre: “Efficacité et évolution de la réponse lymphocytaire T CD8 dans le contexte de l’infection à VIH-1”

Project entitled: “Impact of type-I interferons on melanocytes phenotype and function in vitiligo”. RESUME: “Vitiligo is an auto-immune skin depigmenting disease characterized by the loss of epidermal melanocytes, the skin pigmenting cells. Previous studies have shown that melanocytes in vitiligo are associated with an increased level of oxidative stress leading to the expression of senescence-associated genes. Moreover, our data revealed that type I interferon-related pathways are consistently increased in vitiligo perilesional skin. However, the role of type I interferons is not fully understood. My Ph.D. project aims to decipher the impact of type I interferon (IFN-α and IFN-β) on melanocyte phenotype and function during vitiligo pathogenesis. As previously described, vitiligo skin is infiltrated with IFN-α producing plasmacytoid dendritic cells. Our results show that keratinocytes stimulated with Toll-Like Receptor 3 agonists produce IFN-β. In addition, the expression of interferon-alpha receptor (IFNAR) by melanocytes is increased in perilesional skin of active vitiligo patients as compared to healthy controls and patients with stable disease. The expression of senescence markers such as cyclin-dependent kinase inhibitors p16INK4a and p21CIP/WAF1 is also increased in vitiligo skin as compared to healthy skin. In vitro experiments revealed that melanocytes express a functional IFNAR. IFN-α and IFN-β treated melanocytes show cell cycle arrest, increased expression of Senescence Associated Beta-galactosidase, phosphorylated-p53, p16INK4a, and p21CIP/WAF1. Furthermore, levels of IL-6 and IGFBP-3, two major components of the senescence-associated secretory phenotype, were increased in the presence of type I IFNs. Taken together, our results suggest that type I interferons induce a senescence-like phenotype in melanocytes”. Keywords: vitiligo, melanocyte, type I interferon, senescence

PhD defence (in french)

PhD defence (in french) Titre: “O-GlcNAcylation impact on the physiopathology of systemic lupus erythematosus”

HDR defence (in french) Title: “Physiopathologie de la GVH chronique”