JAK-STAT signaling in asthma

The past two decades have witnessed a dramatic increase in the prevalence of asthma worldwide (1). Asthma is a chronic disease characterized by variable airway obstruction, airway hyperresponsiveness (AHR), and airway inflammation and remodeling. Histological studies show that airways of asthmatic patients contain a chronic inflammatory infiltrate composed of lymphocytes, eosinophils, and mast cells. This infiltrate is usually accompanied by desquamation of the bronchial epithelial layer, goblet cell hyperplasia, and thickening of the submucosa. In most cases, the asthmatic inflammatory process results from inappropriate immune responses to common environmental antigens in a genetically susceptible individual (2). These inappropriate immune responses are orchestrated by a subset of CD4+ T helper cells termed T helper 2 (Th2) cells. Cytokines play a pivotal role in the development of asthma by regulating the expansion of Th2 cells and by mediating many of the Th2 effector functions that underlie the pathogenic events of an asthmatic response. Much effort has recently been placed in elucidating the pathways used by cytokines to mediate their actions. These studies have revealed that cytokine-mediated signals are primarily transduced by the Jak-Stat signaling cascade (3). In this review we will highlight the recent advances made in dissecting the roles of this signaling pathway in the pathogenesis of asthma.