STAT4 activation in smokers and patients with chronic obstructive pulmonary disease

Abstract

Activation of the transcription factor signal transducer and activator of transcription (STAT)-4 is critical for the differentiation of T-helper 1 cells/type-1 cytotoxic T-cells and the production of interferon (IFN)-c.Expression of STAT4, phospho-STAT4, IFN-c and T-box expressed in T-cells (Tbet) proteins in bronchial biopsies and bronchoalveolar lavage (BAL)-derived lymphocytes, obtained from 12 smokers with mild/moderate chronic obstructive pulmonary disease (COPD) (forced expiratory volume in one second (FEV1) 59¡16% predicted), 14 smokers with normal lung function (FEV1 106¡12% pred) and 12 nonsmoking subjects (FEV1 111¡14% pred), was examined by immunohistochemistry and immunocytochemistry.In bronchial biopsies of COPD patients, the number of submucosal phospho- 6103 ). In all smokers who underwent lavage, phospho-STAT4z lymphocytes correlated with airflow obstruction and the number of IFNcz lymphocytes. T-bet expression was not altered in bronchial biopsies and BAL-derived lymphocytes between the three groups.In conclusion, this study suggests that stable mild/moderate chronic obstructive pulmonary disease is associated with an active T-helper 1 cell/type-1 cytotoxic T-cell inflammatory process involving activation of signal transducer and activator of transcription 4 and interferon-gamma production.

Local and systemic cellular inflammation and cytokine release in chronic obstructive pulmonary disease

“…The reason for this IFN-γ production is not clear at present but is likely to reflect ongoing immune response towards microbial agents although arguments also exist to support auto-immune mechanisms [7]. Our results are in keeping with those of Di Stefano et al who reported greater IFN-γ expression in bronchial biopsies of COPD patients [11].…”

Peripheral T Cell Functions Correlate with the Severity of Chronic Obstructive Pulmonary Disease

“…2B) also appear to be an unprecedented finding and a possible result of the power afforded by study of comparatively greater subject numbers. Moreover, this particular observation is also consistent with previous findings of increased activations of in situ T cells within COPD lungs (2,3,7,9). Proportions of circulating CD4 T cells were also seen here to decrease among those more severe COPD (Fig.…”

“…A growing body of evidence suggests that adaptive immune responses play an important role in the pathogenesis and progression of COPD, as evidenced by correlations of lung histological and morphometric measurements with the characteristics of intrapulmonary lymphocyte infiltrations (2)(3)(4)(5)(6)(7)(8)(9)(10). Moreover, activated T cells can cause a variety of the tissue injuries that typify COPD by direct cytopathic effects, elaboration of diverse proinflammatory and deleterious mediators, and/or recruitment and activation of other immune and parenchymal effector cells (11,12).…”

Oligoclonal CD4+T Cells in the Lungs of Patients with Severe Emphysema

“…Hogg and colleagues (8) reported an association between disease severity and small airways containing CD4 ϩ T cells. In bronchial biopsies from patients with mild to moderate COPD, Di Stefano and colleagues (26) reported an increase in IFN-␥ and signal transducer and activator of transcription 4 (STAT4)-expressing cells as compared with control samples. Nuclear STAT4 expression was mostly found in the CD4 ϩ rather than CD8 ϩ T cells.…”