Department of Cardiology and Nephrology, 260th Hospital of the PLA, Shijiazhuang 050041, China.
Autoimmun Rev. 2012 Oct;11(12):844-51. doi: 10.1016/j.autrev.2012.02.019. Epub 2012 Mar 1.
Th17 cells selectively produce the signature cytokines such as IL-17, IL-21 and IL-22, and play a critical role for the chronic inflammatory response and subsequent tissue damage in synovial joints of patients with rheumatoid arthritis (RA). The preliminary clinical study indicates that IL-17 neutralizing therapy can ameliorate inflammatory cascades within peripheral synovial joints in the major population of patients with active RA. Multiple cellular and molecular modulations for the Th17-cell-polarized responses could exist, however, in the inflamed synovium, possibly resulting in a functional niche for the generation and activation of pathogenic Th17 cells. This might establish a vicious cycle culminating in the striking marginal erosions of cartilage and bone in the RA joints, and at least partially abrogate the potential therapeutic benefits related to IL-17 antagonizing or Th17-cell depleting therapy. This article is aimed to discuss the cellular and molecular pathways critically involved in the expansion and activation of pathogenic Th17 cells in RA synovium, with emphasis on the potential therapeutic implications for targeting these pathways to the present and future RA clinics.
辅助性 T 细胞 17（Th17）细胞选择性地产生特征性细胞因子，如白细胞介素-17（IL-17）、IL-21 和 IL-22，并在类风湿关节炎（RA）患者的滑膜关节中慢性炎症反应和随后的组织损伤中发挥关键作用。初步临床研究表明，IL-17 中和疗法可以改善活动期 RA 患者大多数人群外周滑膜关节内的炎症级联反应。然而，在炎症滑膜中可能存在针对 Th17 细胞极化反应的多种细胞和分子调节，从而导致致病性 Th17 细胞的产生和激活的功能龛位。这可能会形成一个恶性循环，最终导致 RA 关节软骨和骨的明显边缘侵蚀，并且至少部分消除与 IL-17 拮抗或 Th17 细胞耗竭疗法相关的潜在治疗益处。本文旨在讨论在 RA 滑膜中参与致病性 Th17 细胞扩增和激活的细胞和分子途径，并强调针对这些途径进行治疗的潜在治疗意义，以应用于当前和未来的 RA 临床治疗。
