Infection & Inflammation, UMR 1173, Inserm, UVSQ/Université Paris Saclay, 2 ave de la Source de la Bièvre, 78180, Montigny-le-Bretonneux, France.
Laboratoire d'Excellence Inflamex, Université Paris Descartes, Sorbonne-Paris-Cité, Paris, France.
Semin Immunopathol. 2021 Apr;43(2):207-219. doi: 10.1007/s00281-020-00832-x. Epub 2021 Jan 15.
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 TGFβ/BMP family of mediators. On the other hand, several spontaneous, inducible, and/or genetically modified mouse models-including SKG mouse, TNF mouse and IL-23-inducible mouse model of SpA-have highlighted the importance of TNFα 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.
了解强直性脊柱炎（SpA）等疾病的复杂发病机制可能受益于研究动物模型。已经开发出了几种合适的模型，特别是为了研究导致 SpA 的遗传因素的作用，包括 HLA-B27、ERAP1 和与白细胞介素（IL）-23/IL-17 轴相关的基因。这种研究的一个最佳范例是 HLA-B27 转基因大鼠模型，该模型促进了关于 HLA-B27 致病性的原始理论的出现，包括先天免疫失调、适应性免疫系统对慢性炎症的贡献以及微生物组对疾病发展的影响。最近，一种新的 HLA-B27 转基因果蝇模型帮助进一步扩展了其中一些理论，涉及 TGFβ/BMP 介质家族。另一方面，几种自发性、诱导性和/或基因修饰的小鼠模型——包括 SKG 小鼠、TNF 小鼠和 SpA 的 IL-23 诱导性小鼠模型——强调了 TNFα 和 IL-23/IL-17 轴在 SpA 表现发展中的重要性。总之，这些动物模型不仅提供了研究疾病机制的机会，还提供了研究潜在治疗靶点的机会。
