Up-regulated integrinα4β1 on systemic lymphocytes and serum IL-17A in interstitial pneumonia

Clin Respir J. 2016 Nov;10(6):722-730. doi: 10.1111/crj.12277. Epub 2015 Mar 3.

Abstract

Background and aims: In interstitial pneumonia (IP), lymphocytes play an important role in lung injury and the involvement of integrinα4β1 on leukocytes has previously been reported in animal models. Although the integrinα4β1 expression level is known to be up-regulated by inflammatory cytokines, the involvement of interleukin (IL)-17A is unclear. The purpose of this study is to address the possible involvement of integrinα4β1 on circulating lymphocytes and its correlation with serum IL-17A in interstitial lung diseases (ILDs).

Methods: We measured the expression levels of integrinα4β1 on peripheral lymphocytes and the serum concentration of IL-17A and IL-23 in subjects with ILDs (n = 27; 14 males and 13 females, 66.7 ± 7.8 years old) and control subjects (n = 10; 5 males and 5 females, 66.6 ± 4.6 years old).

Results: Recombinant IL-17A up-regulated expression levels of integrinα4β1 on healthy human lymphocytes in an in vitro experiment. Expression levels of integrinα4β1 were significantly higher in those with acute hypersensitivity pneumonitis (HP) and non-specific IP (NSIP) compared with control. Serum IL-17A concentration was also significantly increased in acute HP and NSIP subjects compared with control. And IL-17A concentration positively correlated with integrinα4β1 expression level (P < 0.05). Serum IL-23 was below the minimal detectable level in all subjects.

Conclusions: These findings suggest that up-regulated levels of integrinα4β1 on systemic lymphocytes and elevated serum IL-17A might be involved in the extravasation of lymphocytes in IP.

Keywords: IL-17A; integrinα4β1; interstitial lung disease.

MeSH terms

  • Aged
  • Female
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Integrin alpha4beta1 / metabolism*
  • Interleukin-17 / blood*
  • Interleukin-23 Subunit p19 / blood
  • Lung Diseases, Interstitial / blood
  • Lung Diseases, Interstitial / immunology*
  • Lymphocytes / immunology*
  • Male
  • Middle Aged
  • Up-Regulation

Substances

  • IL17A protein, human
  • IL23A protein, human
  • Integrin alpha4beta1
  • Interleukin-17
  • Interleukin-23 Subunit p19