In Vivo Models for Inflammatory Arthritis
In vivo mouse models of inflammatory arthritis are extensively used to investigate pathogenic mechanisms governing inflammation-driven joint damage. Two commonly utilized models include collagen-induced arthritis (CIA) and methylated bovine serum albumin (mBSA) antigen-induced arthritis (AIA). These offer unique advantages for modeling different aspects of human disease. CIA involves breach of immunological tolerance resulting in systemic autoantibody-driven arthritis, while AIA results in local resolving inflammatory flares and articular T cell-mediated damage. Despite limitations that apply to all animal models of human disease, CIA and AIA have been instrumental in identifying pathogenic mediators, immune cell subsets and stromal cell responses that determine disease onset, progression, and severity. Moreover, these models have enabled investigation of disease phases not easily studied in patients and have served as testing beds for novel biological therapies, including cytokine blockers and small molecule inhibitors of intracellular signaling that have revolutionized rheumatoid arthritis treatment.
Key wordsInflammatory arthritis Rheumatoid arthritis Collagen-induced arthritis Antigen-induced arthritis Histopathology
G.J. is supported by an Arthritis Research UK Career Development Fellowship (20305). D.H. is supported by a Medical Research Council PhD studentship and Life Science Research Network Wales, an initiative funded through the Welsh Government’s Ser Cymru program. K.S. is supported by a PhD studentship funded through a generous donation from The Elizabeth Owens Bequest at Cardiff University.
- 1.Smolen JS, Aletaha D, McInnes IB (2016) Rheumatoid arthritis. Lancet S0140-6736:30173–30178Google Scholar
- 18.Nickdel MB, Conigliaro P, Valesini G, Hutchison S, Benson R, Bundick RV, Leishman AJ, McInnes IB, Brewer JM, Garside P (2009) Dissecting the contribution of innate and antigen-specific pathways to the breach of self-tolerance observed in a murine model of arthritis. Ann Rheum Dis 68:1059–1066CrossRefPubMedGoogle Scholar
- 19.Nowell MA, Williams AS, Carty SA, Scheller J, Hayes AJ, Jones GW, Richards PJ, Slinn S, Ernst M, Jenkins BJ, Topley N, Rose-John S, Jones SA (2009) Therapeutic targeting of IL-6 trans signaling counteracts STAT3 control of experimental inflammatory arthritis. J Immunol 182:613–622CrossRefPubMedGoogle Scholar
- 21.Jones GW, Bombardieri M, Greenhill CJ, McLeod L, Nerviani A, Rocher-Ros V, Cardus A, Williams AS, Pitzalis C, Jenkins BJ, Jones SA (2015) Interleukin-27 inhibits ectopic lymphoid-like structure development in early inflammatory arthritis. J Exp Med 212:1793–1802CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Vingsbo C, Sahlstrand P, Brun JG, Jonsson R, Saxne T, Holmdahl R (1996) Pristane-induced arthritis in rats: a new model for rheumatoid arthritis with a chronic disease course influenced by both major histocompatibility complex and non-major histocompatibility complex genes. Am J Pathol 149:1675–1683PubMedPubMedCentralGoogle Scholar