Regulation of IL-17 in chronic inflammation in the human lung

Clin Sci (Lond). 2011 Jun;120(12):515-24. doi: 10.1042/CS20100417.

Abstract

The regulation of human Th17 cell effector function by Treg cells (regulatory T-cells) is poorly understood. In the present study, we report that human Treg (CD4(+)CD25(+)) cells inhibit the proliferative response of Th17 cells but not their capacity to secrete IL (interleukin)-17. However, they could inhibit proliferation and cytokine production by Th1 and Th2 cells as determined by IFN-γ (interferon-γ) and IL-5 biosynthesis. Currently, as there is interest in the role of IL-17-producing cells and Treg cells in chronic inflammatory diseases in humans, we investigated the presence of CD4(+)CD25(+) T-cells and IL-17 in inflammation in the human lung. Transcripts for IL-17 were expressed in mononuclear cells and purified T-cells from lung tissue of patients with chronic pulmonary inflammation and, when activated, these cells secrete soluble protein. The T-cell-specific transcription factors RORCv2 (retinoic acid-related orphan receptor Cv2; for Th17) and FOXP3 (forkhead box P3; for Treg cells) were enriched in the T-cell fraction of lung mononuclear cells. Retrospective stratification of the patient cohort into those with COPD (chronic obstructive pulmonary disease) and non-COPD lung disease revealed no difference in the expression of IL-17 and IL-23 receptor between the groups. We observed that CD4(+)CD25(+) T-cells were present in comparable numbers in COPD and non-COPD lung tissue and with no correlation between the presence of CD4(+)CD25(+) T-cells and IL-17-producing cells. These results suggest that IL-17-expressing cells are present in chronically inflamed lung tissue, but there is no evidence to support this is due to the recruitment or expansion of Treg cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • CD4-Positive T-Lymphocytes / immunology*
  • Child
  • Chronic Disease
  • Female
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-17 / metabolism
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Male
  • Middle Aged
  • Pneumonia / immunology*
  • Pneumonia / metabolism*
  • Pulmonary Disease, Chronic Obstructive / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • Interleukin-17
  • Interleukin-2 Receptor alpha Subunit
  • Interferon-gamma