Non-MHC Risk Alleles in Rheumatoid Arthritis and in the Syntenic Chromosome Regions of Corresponding Animal Models

The involvement of autoreactive T cells in the pathogenesis of rheumatoid arthritis (RA) as well as in autoimmune animal models of arthritis has been well established; however, unanswered questions, such as the role of joint-homing T cells, remain. Animal models of arthritis are superb experimental tools in demonstrating how T cells trigger joint inflammation, and thus can help to further our knowledge of disease mechanisms and potential therapies. In this Review, we discuss the similarities and differences in T-cell subsets and functions between RA and mouse arthritis models. For example, various T-cell subsets are involved in both human and mouse arthritis, but differences might exist in the cytokine regulation and plasticity of these cells. With regard to joint-homing T cells, an abundance of synovial T cells is present in humans compared with mice. On the other hand, local expansion of type 17 T helper (TH17) cells is observed in some animal models, but not in RA. Finally, whereas T-cell depletion essentially failed in RA, antibody targeting of T cells can work, at least preventatively, in most arthritis models. Clearly, additional human and animal studies are needed to fill the gap in our understanding of the specific contribution of T-cell subsets to arthritis in mice and men.

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“…20,114 Some of these mouse loci overlap between the two models as well as with RA susceptibility alleles. 20,114 …”

Section: Rise and Persistence Of Autoreactive T Cellsmentioning

confidence: 99%

Of mice and men: how animal models advance our understanding of T-cell function in RA

et al. 2014

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“…In spite of the advanced age of these animals, no spontaneous arthritis was observed. According to Besenyei et al [ 26 ], approximately 0.5 to 1.0% of retired breeder BALB/c mice can develop the disease spontaneously.…”

Section: Discussionmentioning

confidence: 99%

Commercial Bovine Proteoglycan Is Highly Arthritogenic and Can Be Used as an Alternative Antigen Source for PGIA Model

Ishikawa

Colavite

Rosa

et al. 2014

BioMed Research International

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Rheumatoid arthritis (RA) is the most common systemic autoimmune disease. It affects mainly the joints, causing synovitis, cartilage destruction, and bone erosion. Many experimental models are used to study the mechanisms involved in immunopathogenesis and new therapies for this disease. Proteoglycan-induced arthritis (PGIA) is a widely used model based on the cross-reactivity of injected foreign (usually human) PG and mice self-PG. Considering the complexity of the extraction and purification of human PG, in this study we evaluated the arthritogenicity of bovine PG that is commercially available. Bovine PG was highly arthritogenic, triggering 100% incidence of arthritis in female BALB/c retired breeder mice. Animals immunized with bovine PG presented clinical symptoms and histopathological features similar to human RA and other experimental models. Moreover, bovine PG immunization determined higher levels of proinflammatory and anti-inflammatory cytokines in arthritic mice compared to healthy ones. As expected, only the arthritic group produced IgG1 and IgG2a antibodies against PG. Thus, commercial bovine PG can be used as an alternative antigenic source to PGIA for the study of many RA aspects, including the immunopathogenesis of the disease and also the development of new therapies.

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“…There are numerous rodent models that simulate some or many of the clinical, immunological, or histopathological features of the disease. It has become a strong working hypothesis that MHC and non-MHC genetic components share loci that are common in various autoimmune diseases and in corresponding animal models [ 62 ]. The most relevant animal models of rheumatoid arthritis appear to be those induced by cartilage matrix components such as PG aggrecan or type II collagen [ 63 – 65 ].…”

Section: Rheumatoid Arthritis (Ra) and Its Experimental Animal Modmentioning

confidence: 99%

Proteoglycan Aggrecan Conducting T Cell Activation and Apoptosis in a Murine Model of Rheumatoid Arthritis

Hanyecz

Olasz

Tarjányi

et al. 2014

BioMed Research International

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Rheumatoid arthritis (RA) is a systemic autoimmune disease and its targeting of the joints indicates the presence of a candidate autoantigen(s) in synovial joints. Patients with RA show immune responses in their peripheral blood to proteoglycan (PG) aggrecan. One of the most relevant animal models of RA appears to be proteoglycan-induced arthritis (PGIA), and CD4+ T cells seem to play a crucial role in the initiation of the disease. In this review, the role of various T cell epitopes of aggrecan in the induction of autoreactive T cell activation and arthritis is discussed. We pay special attention to two critically important arthritogenic epitopes, 5/4E8 and P135H, found in the G1 and G3 domains of PG aggrecan, respectively, in the induction of autoimmune arthritis. Finally, results obtained with the recently developed PG-specific TCR transgenic mice system showed that altered T cell apoptosis, the balance of activation, and apoptosis of autoreactive T cells are critical factors in the development of autoimmunity.

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Non-MHC Risk Alleles in Rheumatoid Arthritis and in the Syntenic Chromosome Regions of Corresponding Animal Models

Cited by 10 publications

References 134 publications

Of mice and men: how animal models advance our understanding of T-cell function in RA

Of mice and men: how animal models advance our understanding of T-cell function in RA

Commercial Bovine Proteoglycan Is Highly Arthritogenic and Can Be Used as an Alternative Antigen Source for PGIA Model

Proteoglycan Aggrecan Conducting T Cell Activation and Apoptosis in a Murine Model of Rheumatoid Arthritis

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