Dr. Jean Fletcher

  Autoimmune Diseases (Multiple Sclerosis, Rheumatoid Arthritis)   Autoimmunity   HIDRADENITIS SUPPURATIVA   IMMUNE FUNCTION   Immune regulation   Immune system   IMMUNE-RESPONSE   IMMUNITY   Immunoassays   IMMUNOLOGICAL MECHANISMS   IMMUNOLOGICAL REGULATION   Immunology   Immunology, Immunotherapy   Immunotherapy   Multiple Sclerosis   MULTIPLE-SCLEROSIS   Regulatory T cells   Rheumatology and rheumatological disorders   T cells   Th17 cells   Tumour Biology/ Immunology

Th17 cells are key players in autoimmune/inflammatory diseases and an important therapeutic target. My independent research career has focused on understanding the regulation of Th17 cells in human diseases. 20/65 articles have been cited >100 times, indicating the significant impact of my research. I have established clinical collaborations which have underpinned the translational aspects of my work. My overarching research aim is to understand the role of Th17 cells in human disease and how they can be targeted therapeutically. My early work into the role of Th17 cells in MS made a significant impact by dissecting the regulation of IL-17 by different types of regulatory T (Treg) cells and demonstrated defective regulation in MS patients. Subsequent work showed how pathogenic Th17 cells in MS patients were inhibited by IFN-ß therapy. Our research into Th17 cells in RA demonstrated that Th17 cells in the RA joint are highly inflammatory and resistant to regulation. Th17 cells were unstable and switched into a highly pathogenic ex-Th17 phenotype, potentially explaining the lack of success of anti-IL-17 therapies in RA. We demonstrated differential regulation of Th17 vs Treg cells by metabolic pathways, allowing for therapeutic manipulation. We also showed that T cells induced a switch towards glycolysis in RA synovial fibroblasts and that targeting glycolysis could reverse these inflammatory effects. More recently, our research into HS revealed several therapeutic targets which can reduce inflammation in HS. We identified Th17 cells as a key target, and indeed the first anti-IL-17A drug was recently licensed for HS. We showed that inflammation/Th17 cells in HS could be targeted using metformin and inhibitors of the NLRP3 inflammasome. Given that metformin is a cheap drug and inflammasome inhibitors are currently in clinical development, these findings are significant as HS is a disease with a high unmet need for effective therapies.