Lessons on SpA pathogenesis from animal models

Abstract

Understanding the complex mechanisms underlying a disorder such as spondyloarthritis (SpA) may benefit from studying animal models. Several suitable models have been developed, in particular to investigate the role of genetic factors predisposing to SpA, including HLA-B27, ERAP1 and genes related to the interleukin (IL)-23/IL-17 axis. One of the best examples of such research is the HLA-B27 transgenic rat model that fostered the emergence of original theories regarding HLA-B27 pathogenicity, including dysregulation of innate immunity, contribution of the adaptive immune system to chronic inflammation and influence of the microbiota on disease development. Very recently, a new model of HLA-B27 transgenic Drosophila helped to expand further some of those theories in an unexpected direction involving the TGF/BMP family of mediators. On the other hand, several spontaneous, inducible and/or genetically modified mouse models -including SKG mouse, TNF are mouse and IL-23-inducible mouse model of SpA-have highlighted the importance of TNF and IL-23/IL-17 axis in the development of SpA manifestations. Altogether, those animal models afford not only to study disease mechanism but also to investigate putative therapeutic targets.

Levofloxacin induces differential effects in the transcriptome between the gut, peripheral and axial joints in the Spondyloarthritis DBA/1 mice: Improvement of intestinal dysbiosis and the overall inflammatory process

“…Follow-ups of patients with food poisoning caused by arthritogenic bacteria confirm that a proportion of infected individuals develop complete ReA; a subset of these patients evolve to AS. However, several rodent models fail to develop SpA if raised in germ-free conditions suggesting that the microbiota is critical for the development of arthritis [ 12 ].…”

“…Furthermore, because the confined young males fight aggressively, bacterial dissemination from the resultant skin wounds could possibly induce or perpetuate arthritis/enthesitis. To our knowledge, intestinal inflammation has not been described in DBA/1 mice [ 12 ]. Given the pathogenic connection between intestinal inflammation, dysbiosis, and joint inflammation in patients with SpA, a detailed exploration of this link in the DBA/1 mice is essential to assess the influence of bacterial communities in the gut and joints.…”

“…Housing rodents in germ-free conditions precludes the onset of arthritis; however, when the rodents grow in a non-sterile environment, arthritis develops. Instead of active infections by pathogenic bacteria, arthritis has been linked to specific profiles in the commensal microbiota [12][13][14]. Specific bacteria allegedly play either a favorable or detrimental role in arthritis; however, in animal models of arthritis, the results vary significantly between different animal models of arthritis [15][16][17].…”

Rodent Models of Spondyloarthritis Have Decreased White and Bone Marrow Adipose Tissue Depots

“…To assess how chronic inflammation may affect BMAT, we utilized HLA-B27 transgenic rats (B27) and curdlan-challenged SKG mice, two well-established models of SpA (18). Both models recapitulate typical features of human SpA, including chronic systemic inflammation and accelerated bone loss and reduced bone strength due to stimulation of osteoclastogenesis and suppression of bone formation (19)(20)(21).…”

Recent advances in spondyloarthritis: positive developments in the seronegative domain

“…Defining the immunopathology of entheseal tissues as well as target sites such as the sacroiliac joints has been challenged by the relative inaccessibility of these tissues, particularly in axial SpA. In this regard, animal models have provided a more controlled setting to define basic immune mechanisms in SpA [4]. The HLA-B27 transgenic rat is one example of capitalizing on insights from genetic research in SpA to develop translational studies to evaluate immune consequences of genetic elements conferring susceptibility to SpA.…”