A curious feature of axial disease in ankylosing spondylitis (AS) and related non-radiographic axial spondyloarthropathy (nrAxSpA) is that spinal inflammation may ultimately be associated with excessive entheseal tissue repair with new bone formation. Other SpA associated target tissues including the gut and the skin have well established paradigms on how local tissue immune responses and proven disease relevant cytokines including TNF and the IL-23/17 axis contribute to tissue repair. Normal skeletal homeostasis including the highly mechanically stressed entheseal sites is subject to tissue microdamage, micro-inflammation and ultimately repair. Like the skin and gut, healthy enthesis has resident immune cells including ILCs, γδ T cells, conventional CD4+ and CD8+ T cells and myeloid lineage cells capable of cytokine induction involving prostaglandins, growth factors and cytokines including TNF and IL-17 that regulate these responses. We discuss how human genetic studies, animal models and translational human immunology around TNF and IL-17 suggest a largely redundant role for these pathways in physiological tissue repair and homeostasis. However, disease associated immune system overactivity of these cytokines with loss of tissue repair “fine tuning” is eventually associated with exuberant tissue repair responses in AS. Conversely, excessive biomechanical stress at spinal enthesis or peripheral enthesis with mechanically related or degenerative conditions is associated with a normal immune system attempts at cytokine fine tuning, but in this setting, it is commensurate to sustained abnormal biomechanical stressing. Unlike SpA, where restoration of aberrant and excessive cytokine “fine tuning” is efficacious, antagonism of these pathways in biomechanically related disease may be of limited or even no value.

强直性脊柱炎 (AS) 和相关的非影像学中轴性脊柱关节病 (nrAxSpA) 中轴性疾病的一个奇怪特征是脊柱炎症最终可能与过度的附着点组织修复和新骨形成有关。包括肠道和皮肤在内的其他 SpA 相关靶组织已经建立了关于局部组织免疫反应和已证实的疾病相关细胞因子（包括 TNF 和 IL-23/17 轴）如何促进组织修复的范例。包括高度机械应力的附着点在内的正常骨骼稳态会受到组织微损伤、微炎症和最终修复的影响。与皮肤和肠道一样，健康的附着点也有常驻免疫细胞，包括 ILC、γδ T 细胞、能够诱导细胞因子的常规 CD4+ 和 CD8+ T 细胞和髓系细胞涉及前列腺素、生长因子和细胞因子，包括调节这些反应的 TNF 和 IL-17。我们讨论了围绕 TNF 和 IL-17 的人类基因研究、动物模型和转化人类免疫学如何表明这些途径在生理组织修复和体内平衡中的主要冗余作用。然而，这些细胞因子的疾病相关免疫系统过度活跃与组织修复“微调”的丧失最终与 AS 中旺盛的组织修复反应有关。相反，脊柱附着点或外周附着点的过度生物力学应力与机械相关或退行性疾病与正常免疫系统尝试细胞因子微调有关，但在这种情况下，它与持续的异常生物力学应力相称。与 SpA 不同，在其中恢复异常和过度的细胞因子“微调”是有效的，这些途径在生物力学相关疾病中的拮抗作用可能有限甚至没有价值。