Influence of total glucosides of paeony on PD-1/PD-L1 expression in primary Sjögren's syndrome

Int J Rheum Dis. 2019 Feb;22(2):200-206. doi: 10.1111/1756-185X.13391. Epub 2018 Oct 18.

Abstract

Aim: To study the influence of total glucosides of paeony (TGP) on the expression of peripheral blood programmed cell death protein 1 (PD-1) and its ligand (PD-L1) in patients with primary Sjögren's syndrome (pSS).

Method: Ten patients with new-onset pSS were selected as the experimental group and were treated with 1.8 g of TGP (the main ingredient is Radix Paeoniae Alba) daily for 3 months; furthermore, 10 physically healthy individuals were selected as the control group. Peripheral blood mononuclear cells were isolated, and flow cytometry was used to detect PD-1 expression on the surface of CD4+ T and CD8+ T lymphocytes and PD-L1 expression on the surface of CD14+ monocytes and CD19+ B cells before and after treatment in the experimental and control groups. Furthermore, plasma levels of soluble PD-1 (sPD-1), interleukin (IL)-10, and IL-17A were also determined using enzyme-linked immunosorbent assay.

Results: The PD-1 expression on the surface of CD4+ T and CD8+ T lymphocytes in the peripheral blood of patients with pSS were significantly higher than in the control group (P < 0.001). However, PD-L1 expression on the surface of CD14+ monocytes declined but not significantly (P > 0.05), and PD-L1 expression on the surface of CD19+ B cells increased significantly (P < 0.001). Moreover, sPD-1 and IL-17A levels in the plasma of the experimental group were significantly higher than in the control group (P < 0.001), but the IL-10 level was significantly lower than in the control group (P < 0.001). After TGP treatment, PD-1 expression on the surface of CD4+ T and CD8+ lymphocytes in the peripheral blood of patients with pSS had decreased significantly (P < 0.001); the PD-L1 expression on the surface of CD19+ cells had decreased significantly (P < 0.001); and the PD-L1 expression on the surface of CD14+ monocytes did not differ significantly (P > 0.05). Furthermore, the levels of sPD-1 and IL-17A in plasma had decreased (P < 0.01) and IL-10 levels had increased after TGP treatment (P < 0.01).

Conclusion: PD-1/PD-L1 molecules expressed on the surface of T cells, B cells, and monokaryon participated in the pathogenesis and development of SS through interactions. Therefore, TGP, which may increase the expression of PD-1 and its relevant ligand PD-L1 in the peripheral blood mononuclear cells, may play a role in the pathogenesis and development of SS through the PD-1/PD-L1 pathway by regulating regulatory T cells/T helper cell 17.

Keywords: IL-10 and IL-17A levels; PD-1/PD-L1; primary Sjogren syndrome; sPD-1; total glucosides of paeony.

MeSH terms

  • Adult
  • Aged
  • B7-H1 Antigen / blood*
  • B7-H1 Antigen / immunology
  • Case-Control Studies
  • Female
  • Glucosides / isolation & purification
  • Glucosides / therapeutic use*
  • Humans
  • Immunologic Factors / isolation & purification
  • Immunologic Factors / therapeutic use*
  • Interleukin-10 / blood
  • Interleukin-10 / immunology
  • Interleukin-17 / blood
  • Interleukin-17 / immunology
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Paeonia* / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / therapeutic use*
  • Programmed Cell Death 1 Receptor / blood*
  • Programmed Cell Death 1 Receptor / immunology
  • Sjogren's Syndrome / blood
  • Sjogren's Syndrome / drug therapy*
  • Sjogren's Syndrome / immunology
  • Time Factors
  • Treatment Outcome

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Glucosides
  • IL10 protein, human
  • IL17A protein, human
  • Immunologic Factors
  • Interleukin-17
  • PDCD1 protein, human
  • Plant Extracts
  • Programmed Cell Death 1 Receptor
  • Interleukin-10