The inflammatory disorders collectively termed the seronegative spondyloarthropathies (SpA) include ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, the arthritis associated with inflammatory bowel disease including Crohn's disease and ulcerative colitis, the arthritis related to anterior uveitis, and finally, somewhat controversially Behcet's disease. All of these diseases are associated with SNPs in the IL-23R or the interleukin-23 (IL-23) cytokine itself and related downstream signaling JAK pathway genes and the interleukin-17 (IL-17) pathway. In rheumatoid arthritis, the target of the immune response is the synovium but the SpA disorders target the tendon, ligament, and joint capsule skeletal anchorage points that are termed entheses. The discovery that IL-23R-expressing cells were ensconced in healthy murine enthesis, and other extraskeletal anchorage points including the aortic root and the ciliary body of the eye and that systemic overexpression of IL-23 resulted in a severe experimental SpA, confirmed a fundamentally different immunobiology to rheumatoid arthritis. Recently, IL-23R-expressing myeloid cells and various innate and adaptive T cells that produce IL-17 family cytokines have also been described in the human enthesis. Blockade of IL-23 pathway with either anti-p40 or anti-p19 subunits has resulted in some spectacular therapeutic successes in psoriasis and PsA including improvement in enthesitis in the peripheral skeleton but has failed to demonstrate efficacy in AS that is largely a spinal polyenthesitis. Herein, we discuss the known biology of IL-23 at the human enthesis and highlight the remarkable emerging story of this unique skeletal tissue.

中文翻译：

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白细胞介素23通路的发展：脊柱关节病中脑炎的新兴故事。

炎症性疾病统称为血清阴性脊椎病（SpA），包括强直性脊柱炎（AS），银屑病关节炎（PsA），反应性关节炎，与炎症性肠病（包括克罗恩病和溃疡性结肠炎）相关的关节炎，与前葡萄膜炎相关的关节炎，以及，有些引起争议的白塞氏病。所有这些疾病均与IL-23R或白介素23（IL-23）细胞因子本身中的SNP以及相关的下游信号传导JAK途径基因和白介素17（IL-17）途径有关。在类风湿性关节炎中，免疫反应的目标是滑膜，但SpA疾病的目标是被称为烯醇的肌腱，韧带和关节囊骨骼锚固点。从本质上说，发现表达IL-23R的细胞被健康的鼠科动物及其他骨骼外锚定点（包括主动脉根和睫状体）所吸引，并且系统性过表达IL-23会导致严重的实验性SpA。类风湿关节炎的免疫生物学不同。近来，在人类中也已经描述了表达IL-23R的骨髓细胞以及产生IL-17家族细胞因子的各种先天性和适应性T细胞。用抗p40或抗p19亚基阻断IL-23途径已在牛皮癣和PsA方面取得了一些引人注目的治疗成功，包括改善了外周骨架的炎性反应，但未能证明在主要是脊髓性多囊炎的AS中疗效。在这里