Increased levels of Th17 cells are associated with non-neuronal acetylcholine in COPD patients

Immunobiology. 2014 May;219(5):392-401. doi: 10.1016/j.imbio.2014.01.004. Epub 2014 Jan 25.


T-lymphocytes, including Th17-cells and T-cells expressing acetylcholine (ACh), are key components of systemic inflammation in chronic obstructive pulmonary disease (COPD). We investigated whether ACh promotes Th17 cells in COPD. ACh, IL-17A, IL-22, RORγt, FOXP3 expression and AChIL-17A, AChIL-22, AChRORγt coexpression was evaluated in peripheral blood mononuclear cells (PBMC) from COPD patients (n=16), healthy smokers (HS) (n=12) and healthy control subjects (HC) (n=13) (cultured for 48 h with PMA) by flow cytometry. Furthermore, we studied the effect of Tiotropium (Spiriva®) (100 nM) and Olodaterol (1nM) alone or in combination, and of hemicholinium-3 (50 μM) on AChIL-17A, AChIL-22, AChRORγt, and FOXP3 expression in CD3+PBT-cells of PBMC from COPD patients (n=6) cultured for 48 h with PMA. CD3+PBT-cells expressing ACh, IL-17A, IL-22 and RORγt together with CD3+PBT-cells co-expressing AChIL-17A, AChIL-22 and AChRORγt were significantly increased in COPD patients compared to HC and HS subjects with higher levels in HS than in HC without a significant difference. CD3+FOXP3+PBT-cells were increased in HS than in HC and COPD. Tiotropium and Olodaterol reduced the percentage of CD3+PBT-cells co-expressing AChIL-17A, AChIL-22, and AChRORγt while increased the CD3+FOXP3+PBT-cells in PBMC from COPD patients, cultured in vitro for 48 h, with an additive effect when used in combination. Hemicholnium-3 reduced the percentage of ACh+IL-17A+, ACh+IL-22+, and ACh+RORγt+ while it did not affect FOXP3+ expression in CD3+PBT-cells from cultured PBMC from COPD patients. We concluded that ACh might promote the increased levels of Th17-cells in systemic inflammation of COPD. Long-acting β2-agonists and anticholinergic drugs might contribute to control this event.

Keywords: Anticholinergic drugs; Beta-2 long acting; Systemic inflammation; Th-17 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism*
  • Acetylcholine / pharmacology
  • Aged
  • Aged, 80 and over
  • Benzoxazines / pharmacology
  • Cholinergic Antagonists / pharmacology
  • Female
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Interleukin-17 / metabolism
  • Interleukins / metabolism
  • Intracellular Space / metabolism
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Pulmonary Disease, Chronic Obstructive / immunology*
  • Pulmonary Disease, Chronic Obstructive / metabolism*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Risk Factors
  • Scopolamine Derivatives / pharmacology
  • Th17 Cells / drug effects
  • Th17 Cells / immunology*
  • Th17 Cells / metabolism*
  • Tiotropium Bromide


  • Benzoxazines
  • Cholinergic Antagonists
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-17
  • Interleukins
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Scopolamine Derivatives
  • Acetylcholine
  • olodaterol
  • interleukin-22
  • Tiotropium Bromide