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

Summary Chronic obstructive pulmonary disease ( COPD ) is characterized by an abnormal regulatory T cell ( T reg ) response and increases in T helper type 1 ( T h1) and T h17 cell responses. It is unclear if dysregulation of micro RNA s (mi RNA ) within T reg cells contributes to the abnormal inflammatory response in COPD . In this study, we aimed to compare the mi RNA profile of COPD T reg cells with that of healthy controls and to explore the function of differentially expressed mi RNA s. We first obtained T reg and T effector cells (T eff ) 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 RNA s. Six and 96 mi RNA s were expressed differentially in COPD T reg cells versus   T reg cells of healthy non‐smokers and healthy smokers, whereas no differences were found in mi RNA expression in T eff cells. We found that mi R ‐199a‐5p was repressed by approximately fourfold in T reg cells of COPD patients compared to healthy smokers ( P  < 0·05). In addition, mi R ‐199a‐5p was over‐expressed in T reg cells compared to T eff cells ( P  < 0·001) and had significant over‐representation of its target genes in the T reg 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 T aqMan® 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 T h1 and T h17 response.