Decreased T-bet expression and changes in chemokine levels in adults with asthma

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Abstract
T-bet is a novel transcription factor regulating lineage commitment of T helper (Th) lymphocytes to a predominant Th1 phenotype. Previous studies on T-bet and asthma focused mainly on bronchial biopsy specimens. This study assessed the relationship between T-bet expression and levels of selected chemokines in the peripheral blood of asthmatics. Blood was collected from 24 steroid-naive asthmatics, 39 asthmatics on inhaled corticosteroid and 32 age- and sex-matched controls for assay of T-bet expression, specific IgE and chemokines (interferon-gamma inducible protein-10 (IP-10/CXCL10), monokines induced by interferon-gamma (MIG/CXCL9), monocyte chemotactic protein-1 (MCP-1/CCL2), regulated upon activation normal T cell expressed and secreted (RANTES/CCL5) and interleukin-8 (IL-8/CXCL8) levels. T-bet mRNA expression was assessed by real-time quantitative reverse transcription–polymerase chain reaction (RT–PCR). Chemokine levels were assessed by immunofluorescence flow cytometry. The mean (s.d.) age and forced expiratory volume in 1 s (FEV1)% predicted of the asthmatics were 43·6 (14·6) years and 85·9 (20·0)%, respectively. The median (IQR) T-bet expression after normalization with β-actin was suppressed in asthmatics versus controls [asthmatics 0·71 (0·59) versus controls 1·07 (1·14), P = 0·03].The median (IQR) of plasma RANTES was elevated, whereas IP-10 was suppressed in asthmatics versus controls (RANTES: 13 658·0 (13673·3) versus 6299·5 (19 407·8) pg/ml, P = 0·03; IP-10: 1047·6 (589·8) versus 1306·4 (759·9) pg/ml, P = 0·001). There was a weak and negative correlation between T-bet expression and RANTES level in the asthmatics (r = –0·29, P = 0·032). T-bet could be measured in peripheral blood and its expression was suppressed in asthmatics. This is in keeping with asthma being a predominantly Th2 disease and T-bet probably plays a role in the pathogenesis of asthma. Further studies are needed to explore the potential application of peripheral blood monitoring of T-bet.