High peripheral blood th17 percent associated with poor lung function in cystic fibrosis

PLoS One. 2015 Mar 24;10(3):e0120912. doi: 10.1371/journal.pone.0120912. eCollection 2015.

Abstract

People with cystic fibrosis (CF) have been reported to make lung T cell responses that are biased towards T helper (Th) 2 or Th17. We hypothesized that CF-related T cell regulatory defects could be detected by analyzing CD4+ lymphocyte subsets in peripheral blood. Peripheral blood mononuclear cells from 42 CF patients (6 months-53 years old) and 78 healthy controls (2-61 years old) were analyzed for Th1 (IFN-γ+), Th2 (IL-4+), Th17 (IL-17+), Treg (FOXP3+), IL-10+ and TGF-β+ CD4+ cells. We observed higher proportions of Treg, IL-10+ and TGF-β+ CD4+ cells in CF adults (≥ 18 years old), but not children/adolescents, compared with controls. Within the CF group, high TGF-β+% was associated with chronic Pseudomonas aeruginosa lung infection (p < 0.006). We observed no significant differences between control and CF groups in the proportions of Th1, Th2 or Th17 cells, and no association within the CF group of any subset with sex, CFTR genotype, or clinical exacerbation. However, high Th17% was strongly associated with poor lung function (FEV1 % predicted) (p = 0.0008), and this association was strongest when both lung function testing and blood sampling were performed within one week. Our results are consistent with reports of CF as a Th17 disease and suggest that peripheral blood Th17 levels may be a surrogate marker of lung function in CF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Cystic Fibrosis / complications*
  • Cystic Fibrosis / immunology
  • Female
  • Humans
  • Infant
  • Leukocytes, Mononuclear
  • Lung / immunology
  • Lung / microbiology*
  • Male
  • Middle Aged
  • Pseudomonas Infections / complications*
  • Pseudomonas Infections / diagnosis
  • Pseudomonas Infections / immunology
  • Pseudomonas aeruginosa / isolation & purification*
  • Respiratory Tract Infections / complications*
  • Respiratory Tract Infections / diagnosis
  • Respiratory Tract Infections / immunology
  • Th17 Cells / immunology*
  • Young Adult

Grant support

Royal Hobart Hospital Research Foundation, Clifford Craig Medical Research Foundation, and the School of Medicine, University of Tasmania. The Dr Leon Wescombe Cystic Fibrosis Research Fund provided a scholarship for EM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.