Indoleamine 2,3 dioxygenase-mediated tryptophan catabolism regulates accumulation of Th1/Th17 cells in the joint in collagen-induced arthritis.

Objective: Indoleamine 2,3 dioxygenase (IDO) is a catabolic enzyme that initiates the kynurenine pathway of tryptophan degradation and has immunomodulatory properties. The aim of this study was to investigate the regulation of collagen-induced arthritis by tryptophan catabolism mediated by IDO.

Methods: Arthritis was induced by immunization with type II collagen.

Protocol for the induction of arthritis in C57BL/6 mice.

Collagen-induced arthritis is a well-validated, but strain-dependent mouse model of rheumatoid arthritis, with H-2(q) and H-2(r) strains showing the greatest degree of susceptibility. This protocol describes the induction of arthritis in the C57BL/6 strain (H-2(b)), which forms the genetic background of the majority of genetically modified strains. This protocol involves purification of type II collagen from chicken sternums, immunization of mice, clinical assessment of arthritis and analysis of T- and B-cell responses to type II collagen.

CD200-Fc, a novel antiarthritic biologic agent that targets proinflammatory cytokine expression in the joints of mice with collagen-induced arthritis.

Objective: The CD200 receptor (CD200R) is an inhibitory receptor expressed by myeloid cells that is postulated to play an important role in regulation of the immune system. The purpose of this study was to evaluate the efficacy of a soluble ligand of CD200R in established collagen-induced arthritis (CIA) in mice and to analyze changes in cytokine expression following therapy in order to understand its primary mechanism of action.

Methods: Arthritis was induced in DBA/1 mice, and CD200-Fc fusion protein, an isotype control monoclonal antibody, or TNFR-Fc fusion protein was administered over a period of 10 days (total of 4 doses).

Analysing the effect of novel therapies on cytokine expression in experimental arthritis.

Type II collagen-induced arthritis (CIA) is an animal model of rheumatoid arthritis that has been used extensively to address questions of disease pathogenesis and to validate novel therapeutic targets. Susceptibility to CIA is strongly associated with major histocompatibility complex class II genes, and the development of arthritis is accompanied by a robust T- and B-cell response to type II collagen. The main pathological features of CIA include proliferative synovitis with infiltration of inflammatory cells, pannus formation, cartilage degradation, erosion of bone and fibrosis.

Regulation of arthritis by p53: critical role of adaptive immunity.

Objective: The p53 tumor-suppressor protein is expressed in rheumatoid arthritis synovium, and loss of p53 function through somatic mutation can occur in longstanding disease. Previous studies demonstrated that p53 is protective in murine collagen-induced arthritis (CIA). To determine if adaptive immune responses or synovial effector functions are responsible for this effect, passive models of arthritis were studied in p53 wild-type and knockout mice.