Th17 and MAIT17 cells are associated with severe Recessive Dystrophic Epidermolysis Bullosa: Staphylococcus aureus involvement

Recessive Dystrophic Epidermolysis bullosa (RDEB) is characterized by wounds colonized with Staphylococcus aureus associated with local and systemic inflammation. However, it remains unclear how the immune response and S. aureus interact. A novel proteomic pipeline was used to evaluate over 800 proteins in plasma, resulting in a unique proteomic signature that enabled the differentiation of RDEB patients (n=15); mild phenotype n=5; severe phenotype n=10; median 7 years) and controls (n=18; median 5 years). Immune cell (n= 30 subsets and cytokine-producing cells) and cytokine (n=38) profiling identified a severe inflammatory response and activation of conventional CD4+ T and innate-like T cells as Mucosal-Associated invariant T (MAIT) and gamma delta T cells in RDEB severe patients with increased frequency of IL-17A-producing CD4+ T and MAIT cells. Positive S. aureus cultures from skin of 12 out of 15 RDEB patients allowed whole-genome sequencing of patient's strains and assessment of primary keratinocyte immune response upon bacterial challenge. Conditioned media from keratinocytes challenged with S. aureus strains of severe RDEB patients induced a strong Th17 response. In conclusion, this study uncovers a huge systemic inflammatory response associated with a high level of circulating IL-17A-producing CD4+ T and MAIT cells in RDEB patients and supports the involvement of patient S. aureus strains in biasing the host immune response.