Dissecting differences in joint, tendon sheath and systemic pathology between two murine models of synovial self-tolerance breach: what are the respective roles of T helper-1 and -17 cells? (360G-Wellcome-092306_Z_10_Z)

This project will utilize murine models of early events in rheumatoid arthritis (RA) pathogenesis, to determine any differences in pathology when T-helper type 1 (TH1) or type 17 cells (TH17) respectively, are used to initiate loss of synovial self-tolerance. Arthritis will be induced following transfer of TH1 or TH17 cells that recognize ovalbumin peptide i.e. a joint-irrelevant antigen. It will be determined if the severity and nature of histological lesions differs between the two groups in affected joints, associated tendons and draining lymph nodes. This will include identifying transferred T-helper cells. Other organs and tissues will be examined for inflammatory lesions, as in human RA patients they are not limited to diathrodial joints. Finally, it will be established whether the key products of TH1 and TH17 cells i.e. interferon-g (IFN-g) or interleukin-17 (IL-17) are present, and at what levels. This project, conducted as part of a larger immunological study and with the applicant embedded in a large collaborative team of biomedical researchers, will assist in elucidating different or overlapping roles of T-helper cell types during a self-tolerance loss event. Without this basic information, it will not be possible to develop preventative measures for this painful, common and distressing human disease.