neutralization of il-17 ameliorates uveitis but damages photoreceptors in a murine model of spondyloarthritis中和il-17改善葡萄膜炎,但损害spondyloarthritis感光细胞在小鼠模型.pdfVIP

Kezic et al. Arthritis Research Therapy 2012, 14:R18 /content/14/1/R18 RESEARCH ARTICLE Open Access Neutralization of IL-17 ameliorates uveitis but damages photoreceptors in a murine model of spondyloarthritis 1,2 3 1,4,5* 1,6 Jelena M Kezic , Tibor T Glant , James T Rosenbaum and Holly L Rosenzweig Abstract Introduction: Uveitis, or intraocular inflammatory disease, is a frequent extra-articular manifestation of several forms of arthritis. Despite the frequent co-occurrence of uveitis and arthritis, little is understood of the eye’s predisposition to this disease. We recently described a previously unreported uveitis in a murine model of spondyloarthropathy triggered by autoimmunity to aggrecan, a prominent proteoglycan (PG) macromolecule in cartilage. In contrast to the joint and spine, wherein interferon-gamma (IFNg) deficiency reduced disease, IFNg deficiency worsened uveitis. Given the regulatory role of IFNg on the Th17 response and the current focus of anti- interleukin-17 therapeutics in patients with uveitis and spondyloarthritis, we sought to determine the extent to which interleukin (IL)-17 mediates uveitis in the absence of IFNg. Methods: Antigen specific T cell cytokine production was measured in splenocyte cultures using multiplex-ELISA. Transgenic (Tg) mice expressing the T cell receptor (TCR) recognizing the dominant arthritogenic epitope in the G1 domain of PG (TCR-Tg), also lacking IFNg, were immunized with PG. Mice were then systemically administered an anti-IL-17 neutralizing antibody. The onset and severity of peripheral arthritis was evaluated by clinical scoring criteria and histology. Uveitis was assessed using intravital videomicroscopy, which visualizes leukocyte trafficking