Blunted expression of mi R-199a-5p in regulatory T cells of patients with chronic obstructive pulmonary disease compared to unaffected smokers.

Chronic obstructive pulmonary disease ( COPD) is characterized by an abnormal regulatory T cell ( Treg) response and increases in T helper type 1 ( Th1) and Th17 cell responses. It is unclear if dysregulation of micro RNAs (mi RNA) within Treg cells contributes to the abnormal inflammatory response in COPD. In this study, we aimed to compare the mi RNA profile of COPD Treg cells with that of healthy controls and to explore the function of differentially expressed mi RNAs. We first obtained Treg and T effector cells (Teff) from peripheral blood of non-smokers, unaffected current smokers and COPD current smokers. Then, we assessed their mi RNA expression by microarray analysis followed by real-time reverse transcription-polymerase chain reaction ( RT- PCR) validation of particular mi RNAs. Six and 96 mi RNAs were expressed differentially in COPD Treg cells versus Treg cells of healthy non-smokers and healthy smokers, whereas no differences were found in mi RNA expression in Teff cells. We found that mi R-199a-5p was repressed by approximately fourfold in Treg cells of COPD patients compared to healthy smokers ( P < 0·05). In addition, mi R-199a-5p was over-expressed in Treg cells compared to Teff cells ( P < 0·001) and had significant over-representation of its target genes in the Treg transcriptome, being associated with the transforming growth factor ( TGF)-β activation pathway ( P < 0·01). We also confirmed the function of mi R-199a5p in an in-vitro loss-of-function cell model running TaqMan® arrays of the human TGF-β pathway. These findings suggest that the abnormal repression of mi R-199a-5p in patients with COPD compared to unaffected smokers may be involved in modulating the adaptive immune balance in favour of a Th1 and Th17 response. [ABSTRACT FROM AUTHOR]