Department of Pharmaceutics, Rajiv Academy for Pharmacy , Mathura, Uttar Pradesh 281001 , India
Expert Opin Ther Targets. 2014 May;18(5):581-94. doi: 10.1517/14728222.2014.893295. Epub 2014 Mar 18.
The discovery of IL-7 and thymic stromal lymphopoietin (TSLP) has been a major step in the understanding of arthritis. IL-7 amplifies the inflammation induced by other cytokines, primarily TNF. In animal models of arthritis, inhibition of IL-7 limits inflammation and joint erosion. TSLP is an IL-7-like cytokine that triggers dendritic cell-mediated Th2-type inflammatory responses and is considered as a master switch for allergic inflammation. TSLP is a downstream molecule of TNF-α and as such may be involved in the pathophysiology of inflammatory arthritis.
This review summarizes current knowledge of the role of IL-7 and TSLP derived from both animal models and studies in patients with rheumatoid arthritis (RA). The emergence of IL-7 blockade as a future therapy in RA is highlighted, along with the potential goals and limitations of this therapeutic approach. The write-up also highlights the functional capacities of TSLP in arthritis.
Evidences suggest important roles for IL-7 and TSLP in the pathogenesis of RA and can be viewed as potential therapeutic targets. Regulation of these at genetic level is a promising investigational area. Given the difficulty in reconstituting T cells in patients with RA, therapeutic approaches that minimize the elimination of T cells are likely to be more desirable.
白细胞介素 7(IL-7)和胸腺基质淋巴细胞生成素(TSLP)的发现是理解关节炎的重要一步。IL-7 扩增了其他细胞因子(主要是 TNF)引起的炎症。在关节炎的动物模型中,抑制 IL-7 可限制炎症和关节侵蚀。TSLP 是一种类似白细胞介素 7 的细胞因子,可引发树突状细胞介导的 Th2 型炎症反应,被认为是过敏炎症的主开关。TSLP 是 TNF-α 的下游分子,因此可能参与炎症性关节炎的病理生理学。
这篇综述总结了来自关节炎动物模型和类风湿关节炎(RA)患者研究中关于 IL-7 和 TSLP 作用的最新知识。强调了 IL-7 阻断作为 RA 未来治疗方法的出现,以及这种治疗方法的潜在目标和局限性。该综述还强调了 TSLP 在关节炎中的功能作用。
有证据表明 IL-7 和 TSLP 在 RA 的发病机制中起着重要作用,可以被视为潜在的治疗靶点。在基因水平上调节这些靶点是一个很有前途的研究领域。鉴于 RA 患者中 T 细胞的重建困难,减少 T 细胞消除的治疗方法可能更可取。