Expression of programmed death-1 (PD-1) and its ligand PD-L1 is upregulated in endometriosis and promoted by 17beta-estradiol

Gynecol Endocrinol. 2019 Mar;35(3):251-256. doi: 10.1080/09513590.2018.1519787. Epub 2018 Oct 16.

Abstract

The programmed death-1 (PD-1)/PD-L1 pathway plays important roles in immune responses and peripheral tolerance. Under pathological conditions, this pathway can suppress protective T cell responses and induce immune system disorders. Endometriosis (EM) is an estrogen-dependent, immune-associated disease. The expression of PD-1 and PD-L1 has been studied in a variety of cancers and autoimmune diseases. Few studies, however, have attempted to explore their expression and the possibility that they are regulated by estrogen in EM. Eutopic and ectopic endometria and blood samples were collected from 15 women with EM and 15 women without EM. PD-1/PD-L1 expression in endometrial tissues was detected using immunohistochemistry and western blot analysis. Their expression in blood was detected using flow cytometry. In addition, their expression was evaluated in endometrial cells after estrogen and cytokine treatment. We observed PD-1/PD-L1 expression in both eutopic and ectopic endometria, with elevated expression in EM. Their expression was also higher in CD4+/CD8+ T cells in blood from EM patients. In addition, treatment with 17β-estradiol upregulated PD-L1 expression in eutopic epithelial cells in EM. These data suggest that the PD-1/PD-L1 pathway may be involved in EM immune dysfunction and be regulated by estrogen.

Keywords: Programmed death-1; endometriosis; estrogen; immune tolerance; programmed death-ligand 1.

MeSH terms

  • Adult
  • B7-H1 Antigen / metabolism*
  • CD8-Positive T-Lymphocytes / metabolism
  • Endometriosis / metabolism*
  • Endometrium / drug effects
  • Endometrium / metabolism*
  • Estradiol / pharmacology*
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Middle Aged
  • Programmed Cell Death 1 Receptor / metabolism*
  • Up-Regulation*

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Estradiol