Triptolide inhibits the proinflammatory potential of myeloid-derived suppressor cells via reducing Arginase-1 in rheumatoid arthritis

作者：Zhao, Ziling; Huang, Huijie; Ke, Sikai; Deng, Bishun; Wang, Yun-xiu; Xu, Ning; Peng, Anping; Han, Guang; Liang, Enyu; He, Xiaohong; He, Qinglian; Ke, Pei-feng; Huang, Xian-zhang^*; He, Min^*

来源：International Immunopharmacology, 2024, 127: 111345.

DOI：10.1016/j.intimp.2023.111345

• Rheumatoid arthritis
• Myeloid -derived suppressor cells
• Triptolide
• Th17 cells
• Arginase-1

Triptolide (TPT) is widely used in the treatment of rheumatoid arthritis (RA). However, its regulatory mechanisms are not fully understood. This study demonstrated that Myeloid-derived suppressor cells (MDSCs) were expanded in both RA patients and arthritic mice. The frequency of MDSCs was correlated with RA disease severity and T helper 17 (Th17) responses. MDSCs from RA patients promoted the polarization of Th17 cells in vitro, which could be substantially attenuated by blocking arginase-1 (Arg-1). TPT inhibited the differentiation of MDSCs, particularly the monocytic MDSCs (M-MDSCs) subsets, as well as the expression of Arg-1 in a dose dependent manner. Alongside, TPT treatment reduced the potential of MDSCs to promote the polarization of IL17+ T cell in vitro. Consistently, TPT immunotherapy alleviated adjuvant-induced arthritis (AIA) in a mice model, and reduced the frequency of MDSCs, M-MDSCs and IL-17+ T cells simultaneously. The presented data suggest a pathogenic role of MDSCs in RA and may function as a novel and effective therapeutic target for TPT in RA.

• 单位
  广州中医药大学; 中山大学