T(H)2 cytokine-associated transcription factors in atopic and nonatopic asthma: Evidence for differential signal transducer and activator of transcription 6 expression

Background: The expression of IL-4 and IL-5 is increased in patients with a topic asthma compared with control subjects and correlates with indices of pulmonary function, In nonatopic asthma the expression of IL-4, unlike IL-5 , fails to correlate with pulmonary function, and compared with their atopi c counterparts, these patients have fewer cells expressing IL-4 receptor (I L-4R), As such, a deficiency in the IL-4 signaling pathway may be implicate d in nonatopic asthma. The transcription factors GATA-3 and cMAF mediate IL -4 and IL-5 synthesis, whereas signal transducer and activator of transcrip tion 6 (STAT-6) is critical for IL-4R signaling. Objective: This study examines the expression profile of these transcriptio n factors in asthma, according to atopic status. Methods: With immunocytoch emistry, the expression of GATA-3, cMAF, and STAT-B protein was determined in sections of bronchial biopsy specimens from patients with atopic asthma (n = 7), patients with nonatopic asthma (n = 8), and control subjects (n = 8), Results: Higher numbers of cells expressing GATA-3 and cMAF were observed i n patients with atopic and those with nonatopic asthma than in control subj ects and patients with tuberculosis (P < .001). There were also more STAT-6 -immunoreactive cells in patients with atopic and those with nonatopic asth ma than in control subjects (P < .0001, P < .05). Notably, however, fewer c ells expressing STAT-6 protein were observed in nonatopic versus atopic ast hma (P < .0001), Conclusions: These results demonstrate the upregulation of GATA-3 and cMAF in both variants of asthma and indicate that reduced IL-4R signaling, becau se of lower STAT-6 expression, may be a feature of nonatopic asthma.