Elevated expression of both mRNA and protein levels of IL-17A in sputum of stable Cystic Fibrosis patients

Abstract

BackgroundT helper 17 (Th17) cells can recruit neutrophils to inflammatory sites through production of IL-17, which induces chemokine release. IL-23 is an important inducer of IL-17 and IL-22 production. Our aim was to study the role of Th17 cells in cystic fibrosis (CF) lung disease by measuring IL-17 protein and mRNA levels and IL-22 and IL-23 mRNA in sputum of clinically stable CF patients and by comparing these levels with healthy controls.MethodsSputum induction was performed in adult CF patients outside of an exacerbation and healthy control subjects. IL-17A protein levels were measured in supernatants with cytometric bead array (CBA) and RNA was isolated and quantitative RT-PCR was performed for IL-17A, IL-22 and IL-23.ResultsWe found significantly higher levels of IL-17A protein and mRNA levels (both: p < 0.0001) and IL-23 mRNA levels (p < 0.0001) in the sputum of CF group as compared to controls. We found very low levels of IL-22 mRNA in the CF group. The levels of IL-17 and IL-23 mRNA were higher in patients chronically infected with Pseudomonas aeruginosa (P. aeruginosa) as compared to those who were not chronically infected with P. aeruginosa. The presence of Staphylococcus aureus (S. aureus) on sputum did not affect the IL-17 or IL-23 levels. There was no correlation between IL-17 or IL-23 levels and FEV1 nor sputum neutrophilia.ConclusionThe elevated levels of IL-17 and IL-23 might indicate that Th17 cells are implicated in the persistent neutrophil infiltration in CF lung disease and chronic infection with P. aeruginosa.

Flagellin Induces Myeloid-Derived Suppressor Cells: Implications for Pseudomonas aeruginosa Infection in Cystic Fibrosis Lung Disease

“…On the basis of our findings, we speculate that flagellin-induced MDSC accumulation in chronic P. aeruginosa infection in CF patients has functional immunological relevance, as ex vivo and in vitro P. aeruginosa-induced MDSCs significantly suppressed both CD4 and CD8 T cell proliferation and dampened Th17 cell responses, which play a vital role in CF lung disease (24)(25)(26)(27)(28)(29)(30)(31). Consequently, MDSCs, as key interface cells between innate and adaptive immunity, may represent a novel therapeutic target in CF and other P. aeruginosa-associated pulmonary diseases, such as chronic obstructive pulmonary disease or ventilator-associated pneumonia.…”

“…CF T cells were found to be prone to a Th2 phenotype, with the CFTR mutation itself and/or chronic infections with P. aeruginosa as possible underlying factors (42,(44)(45)(46). Importantly, recent lines of evidence indicate that Th17 cells and the IL-17 axis-related cytokines IL-22 and IL-23 could play an essential role in recruiting neutrophils to the CF airways and thereby contributing to neutrophil-mediated tissue damage in CF lung disease, thus labeling CF as a "Th17 disease" (24)(25)(26)(27)(28)(29)(30)(31). Th17 cells secrete IL-17 that, in turn, enhances G-CSF and thereby boosts neutrophil mobilization from the bone marrow.…”

Higher infiltration by Th17 cells compared with regulatory T cells is associated with severe acute T-cell-mediated graft rejection

“…Chronic injury is the most common cause of allograft failure after one-year from transplantation and is a significant determinant of long-term allograft outcome (Arndt et al, 2010;Nankivell et al, 2001). Accumulating evidence shows the role of Th17 cells in the progression of chronic injury in various disorders (Decraene et al, 2010;Syrjälä et al, 2010;Hammerich et al, 2011). In kidney transplantation, Th17 cell infiltration hastens clinical chronic rejection in allograft tissue as well (Deteix et al, 2010).…”

MANAGEMENT OF ENDOCRINE DISEASE: Cystic fibrosis-related diabetes: novel pathogenic insights opening new therapeutic avenues

“…Patients with CF have increased glucose fluctuations and hyperglycemia and this may lead to lymphocyte dysfunction (34). A balance between pro-inflammatory T-helper 17 lymphocytes (Th17) that secrete the pro-inflammatory cytokines IL17 and Tc17, and anti-inflammatory regulatory T cells lymphocytes (Tregs) is essential to maintain immunological tolerance and prevent the onset of several autoimmune diseases (35). The Th17 pathway is involved in CF lung inflammation and, interestingly, also in b-cell destruction occurring in type 1 and type 2 diabetes (36).…”