High Peripheral Blood Th17 Percent Associated with Poor Lung Function in Cystic Fibrosis

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.

Updates on T helper type 17 immunity in respiratory disease

“…The murine studies are also difficult to interpret given that Cftr‐ deficient mice do not develop spontaneous lung disease, in contrast to larger animal models such as the CF pig or ferret; hence, these larger animal models may be required to better understand the role of IL‐17 in CF lung inflammation. Consistent with the notion that Th17 cells contribute to disease, it has been reported that high circulating Th17 responses are strongly associated with poorer lung function . Conditional deletion of IL‐17RA or IL‐17RC in the conducting airway of mice attenuates IL‐17‐mediated neutrophil recruitment into the lung, demonstrating that airway epithelium is a key target of IL‐17RA/RC signaling .…”

Pathogenesis, imaging and clinical characteristics of CF and non-CF bronchiectasis

“…Th17 cells, neutrophils and NKT cells are found in abundance in all-cause bronchiectasis compared to healthy controls [92]. While high Th17 infiltrates independently associate with poorer lung function in CF [93], activation of Th17 antigen-specific pathways have been described in non-CF bronchiectasis [94]. IL-17, a central mediator of the Th17 pathway lacks correlation with bronchiectasis disease phenotypes suggestive of the more prominent role that neutrophil-mediated inflammation likely plays in the pathogenesis of bronchiectasis [94].…”

Widespread alterations in the peripheral blood innate immune cell profile in cystic fibrosis reflect lung pathology

“…The primary cause of morbidity and mortality in cystic fibrosis (CF) is destruction of lung tissue, in which the immune system plays a major role. We and others have shown dysregulation of adaptive CD4 + T cells in CF. However, although innate immune cells and their interactions with adaptive immune responses are clearly important in immune dysregulation in CF, there is little information available about the peripheral changes in innate immune cells other than neutrophils.…”