A LIGHT-HVEM/LTβR axis contributes to the fibrosis of intrauterine adhesion

J Reprod Immunol. 2022 Sep:153:103693. doi: 10.1016/j.jri.2022.103693. Epub 2022 Aug 10.

Abstract

Intrauterine adhesion (IUA) is a fibrotic disease, with complex and multifactorial process, causing menstrual disorders, pregnancy loss or infertility. LIGHT (also named TNFSF14), mainly expressed by immune cells, has been reported to be associated with tissue fibrosis. However, the features of immunocyte subsets, the expression and roles of LIGHT and its receptor HVEM (herpes virus entry mediator) and LTβR (lymphotoxin beta receptor) in IUA remain largely unknown. Compared with the control group, we observed increased ratios of CD45+ cells, neutrophils, T cells, macrophages and decreased natural killer cells proportion, and high LIGHT expression on CD4+ T cells and macrophages in IUA endometrium. Further analysis showed there was a positive correlation between upregulated profibrotic factors (e.g., ɑ-smooth muscle actin, transforming growth factor β1) and HVEM in IUA endometrial tissue. More importantly, recombinant human LIGHT protein directly up-regulated the expression of HVEM, LTβR, profibrotic and proinflammatory factors expression in human endometrial stromal cells. These findings reveal abnormal changes of immune cell subsets proportion and the overexpression of LIGHT-HVEM/LTβR axis in IUA endometrium, should contribute to inflammation and fibrosis formation of IUA.

Keywords: Endometrial stromal cell; Fibrosis; HVEM; Intrauterine adhesion; LIGHT.

MeSH terms

  • Actins
  • Female
  • Fibrosis / genetics
  • Humans
  • Lymphotoxin beta Receptor* / genetics
  • Lymphotoxin beta Receptor* / physiology
  • Pregnancy
  • Receptors, Tumor Necrosis Factor, Member 14* / genetics
  • Signal Transduction
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor Ligand Superfamily Member 14* / genetics
  • Uterine Diseases* / genetics
  • Uterine Diseases* / pathology

Substances

  • Actins
  • Lymphotoxin beta Receptor
  • Receptors, Tumor Necrosis Factor, Member 14
  • TNFRSF14 protein, human
  • TNFSF14 protein, human
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor Ligand Superfamily Member 14