Dataset Information

The Th17 pathway in cystic fibrosis lung disease.

ABSTRACT: Cystic fibrosis (CF) is characterized by bronchoalveolar neutrophilia and submucosal lymphocytosis. We hypothesized that Th17 lymphocytes are part of this submucosal infiltrate.Quantification and phenotyping of the lymphocytic infiltrate in the bronchial submucosa of patients with CF (n = 53, of which 20 were newly diagnosed), non-CF bronchiectasis (n = 17), and healthy control subjects (n = 13).We measured IL-17 levels in bronchoalveolar lavage and CD4(+), CD8(+), and IL-17(+) cell counts in endobronchial biopsies. Correlations were made with infection status and other inflammatory markers. Potential cellular sources of IL-17 were determined by double staining.IL-17(+) cell counts (median [interquartile range] cells/mm(2)) were significantly higher in patients with established CF (205 [115-551]) and non-CF bronchiectasis (245 [183-436]) than in control subjects (53 [12-82]) (P < 0.01 for both). Patients with newly diagnosed CF had intermediate counts (171 [91-252]). IL-17-positive CD4(+) T cells, ??T cells, natural killer T cells, and neutrophils were identified. Bronchoalveolar lavage IL-17 levels (pg/ml) were highest in established CF (14.6 [2.2-38.4]), low in newly diagnosed CF and control subjects (1.7 [1.7-1.74]; 1.7 [1.7-3]), and intermediate in non-CF bronchiectasis (9.1 [1.7-34] pg/ml) (Kruskal-Wallis P = 0.001). There was a significant correlation between IL-17 and neutrophil counts (P < 0.001, R = 0.6) as well as IL-4 (P < 0.001, R = 0.84).Th17 lymphocytes are present in the airway submucosa in CF, even in a young, newly diagnosed group. Other IL-17(+) cells include neutrophils, ?? T cells, and natural killer T cells.

SUBMITTER: Tan HL

PROVIDER: S-EPMC3381840 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Th17 pathway in cystic fibrosis lung disease.

Tan Hui-Leng HL Regamey Nicolas N Brown Sarah S Bush Andrew A Lloyd Clare M CM Davies Jane C JC

American journal of respiratory and critical care medicine 20110407 2

<h4>Rationale</h4>Cystic fibrosis (CF) is characterized by bronchoalveolar neutrophilia and submucosal lymphocytosis. We hypothesized that Th17 lymphocytes are part of this submucosal infiltrate.<h4>Objectives</h4>Quantification and phenotyping of the lymphocytic infiltrate in the bronchial submucosa of patients with CF (n = 53, of which 20 were newly diagnosed), non-CF bronchiectasis (n = 17), and healthy control subjects (n = 13).<h4>Methods</h4>We measured IL-17 levels in bronchoalveolar lava ...[more]

PMID: 21474644

Similar Datasets

Project description:Variability in pulmonary disease severity is found in patients with cystic fibrosis (CF) who have identical mutations in the CF transmembrane conductance regulator (CFTR) gene. We hypothesized that one factor accounting for heterogeneity in pulmonary disease severity is variation in the family of genes affecting the biology of interleukin-1 (IL-1), which impacts acquisition and maintenance of Pseudomonas aeruginosa infection in animal models of chronic infection.We genotyped 58 single nucleotide polymorphisms (SNPs) in the IL-1 gene cluster in 808 CF subjects from the University of North Carolina and Case Western Reserve University (UNC/CWRU) joint cohort. All were homozygous for DeltaF508, and categories of "severe" (cases) or "mild" (control subjects) lung disease were defined by the lowest or highest quartile of forced expired volume (FEV(1)) for age in the CF population. After adjustment for age and gender, genotypic data were tested for association with lung disease severity. Odds ratios (ORs) comparing severe versus mild CF were also calculated for each genotype (with the homozygote major allele as the reference group) for all 58 SNPs. From these analyses, nine SNPs with a moderate effect size, OR < or =0.5 or >1.5, were selected for further testing. To replicate the case-control study results, we genotyped the same nine SNPs in a second population of CF parent-offspring trios (recruited from Children's Hospital Boston), in which the offspring had similar pulmonary phenotypes. For the trio analysis, both family-based and population-based associations were performed.SNPs rs1143634 and rs1143639 in the IL1B gene demonstrated a consistent association with lung disease severity categories (P < 0.10) and longitudinal analysis of lung disease severity (P < 0.10) in CF in both the case-control and family-based studies. In females, there was a consistent association (false discovery rate adjusted joint P-value <0.06 for both SNPs) in both the analysis of lung disease severity in the UNC/CWRU cohort and the family-based analysis of affection status.Our findings suggest that IL1beta is a clinically relevant modulator of CF lung disease.

Dataset Information

The Th17 pathway in cystic fibrosis lung disease.

Publications

The Th17 pathway in cystic fibrosis lung disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets