Regulation and Effector function of Th1 and Th17 cells in psoriatic arthritis

• Applicant: Dr. Axel Hueber
• Subject Area: Rheumatology
• Term: from 2007 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 40771724

Psoriatic arthritis (PsA) is a chronic inflammatory disorder affecting joints and entheses [1]. T cells are implicated in pathogenesis by mainly circumstantial data but their direct role is poorly understood. Recently, a new T cell subset, Th17 cells, has been described which plays a pro-inflammatory role in human autoimmune diseases. In preliminary studies we observed juxtaposition of Th1 and Th17 cells in PsA synovium. Understanding the cross-regulation of Th1 and Th17 cells in human inflammation represents an important challenge in cellular immunology, with critical implications for therapeutic targeting of IL-12 superfamily members. This fellowship will characterise Th1 and Th17 cells, and their regulatory cytokines, in PsA synovial and enthesial tissue. Thereafter, it will test in vitro the interaction between Th1 and Th17 cells in effector pathways relevant to PsA pathogenesis, including macrophage activation, osteoblast / osteoclast maturation and fibroblast-like synoviocyte activation. Finally the capacity of Th1 and Th17 cells to cross regulate effector function in vivo will be tested using the OVA-induced arthritis model developed in the host laboratory. Together these studies will significantly enhance our understanding of the interactions between key effector T cell responses in adaptive immunity and will set such observations in the context of PsA pathogenesis.

• DFG Programme: Research Fellowships
• International Connection: United Kingdom
• Host: Professor Dr. Iain B. McInnes