CD39/CD73 and the imbalance of Th17 cells and regulatory T cells in allergic asthma

Mol Med Rep. 2013 Nov;8(5):1432-8. doi: 10.3892/mmr.2013.1692. Epub 2013 Sep 18.

Abstract

In the immune system, CD4+CD25+Foxp3+ regulatory T cells (Tregs) maintain self‑tolerance and Th17 cells mediate inflammatory responses. CD39 is expressed on the surface of a subset of naturally occurring human Tregs that are important in constraining pathogenic Th17 cells. Additional studies have shown that Tregs differentiate into interleukin‑17 (IL‑17)+Foxp3+ T cells. Our previous study indicated an imbalance of Th17 and Tregs in allergic asthma; however, the underlying mechanisms remain poorly understood. Using quantitative PCR (qPCR), CD39 and CD73 mRNA levels in CD4+ T cells were investigated. Flow cytometry was used to analyze the proportion of IL‑17+Foxp3+ T cells, and CD39 and CD73 expressed by CD4+ T cells and Tregs in the peripheral blood of the subjects. The results of the present study demonstrated an increased frequency of CD4+Foxp3+IL‑17+ T cells in moderate to severe asthma. A deficiency in CD39 expressed on the surface of CD4+ T cells and Tregs was observed in asthma patients. The expression of CD39 and CD73 on the surface of CD4+ T cells and Tregs was negatively correlated with the number of Th17 cells. These results indicated that the plasticity of Tregs transforming to IL‑17+Foxp3+CD4+ T cells, the reduced frequency of CD39+ Tregs and less effective suppression of IL‑17 production by residual CD39+ Tregs leads to an imbalance of Th17 and Tregs in asthma. Therefore, enhanced CD39 activity is hypothesized to prevent the progression of asthma.

Publication types

  • Comparative Study

MeSH terms

  • 5'-Nucleotidase / immunology*
  • 5'-Nucleotidase / metabolism
  • Adult
  • Antigens, CD / immunology*
  • Antigens, CD / metabolism
  • Apyrase / immunology*
  • Apyrase / metabolism
  • Asthma / immunology*
  • Asthma / metabolism
  • Asthma / pathology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Case-Control Studies
  • Cell Proliferation
  • Cells, Cultured
  • Female
  • Flow Cytometry
  • GPI-Linked Proteins / immunology
  • GPI-Linked Proteins / metabolism
  • Humans
  • Interleukin-17 / immunology*
  • Interleukin-17 / metabolism
  • Male
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Th17 Cells / immunology*
  • Th17 Cells / metabolism

Substances

  • Antigens, CD
  • GPI-Linked Proteins
  • Interleukin-17
  • RNA, Messenger
  • 5'-Nucleotidase
  • NT5E protein, human
  • Apyrase
  • CD39 antigen