Increased Th17/Treg ratio in chronic liver GVHD

Bone Marrow Transplant. 2014 Apr;49(4):539-44. doi: 10.1038/bmt.2013.215. Epub 2014 Jan 13.

Abstract

The contribution of Th17 cells to chronic GVHD (cGVHD) has been demonstrated in cGVHD mouse models. However, their contribution to human liver cGVHD remains unclear. We evaluated Th17 cells in biopsies from a cohort of 17 patients with liver cGVHD. We observed a significant increase in Th17 cells in the liver of patients with cGVHD, as demonstrated by an increase in CCR6+, CD161+ and RORγt+ T cells (P=0.03, P=0.0001 and P=0.03, respectively). We also assessed the presence of Th1 and regulatory (Treg) T cells: the numbers of Th1 and Treg cells were very low, with no difference between the two groups (P=0.88 and P=0.12, respectively). Furthermore, Th17/Th1 and Th17/Treg ratios were significantly increased in the liver of patients with liver cGVHD (P=0.005 and P=0.002, respectively). This study provides evidence for an infiltration by Th17 cells in the liver of patients with cGVHD and an increased Th17/Treg ratio, suggesting a defect in the regulatory mechanism driven by Treg cells or an inappropriate activation of effectors cells, especially Th17 cells, or both mechanisms, in human liver cGVHD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Biopsy
  • Female
  • Graft vs Host Disease / immunology*
  • Graft vs Host Disease / pathology
  • Humans
  • Liver Diseases / immunology*
  • Liver Diseases / pathology
  • Male
  • Mice
  • Middle Aged
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / pathology*
  • Th17 Cells / immunology
  • Th17 Cells / pathology*