Signal transduction around thymic stromal lymphopoietin (TSLP) in atopic asthma

Atopic asthma is a common inflammatory disorder of the airway epithelium characterized by tissue obstruction and remodeling, bronchial smooth muscle cell hyperreactivity to allergens and chronic bronchial inflammation. It classically involves allergen-driven T helper 2 (Th2) lymphocyte polarisation with coordinate production of interleukin (IL)-4, IL-5, IL-13 and granulocyte-macrophage colony-stimulating factor (GM-CSF), which are encoded in one gene cluster on chromosome 5q31-34 [1]. IL-4 and IL-13 are critically involved in the pathogenesis of allergic asthma by regulating IgE-production by B cells, inducing airway hyperreactivity and triggering key features of airway remodeling, whereas IL-5 is a key factor for eosinophilia [2,3]. Activation of IgE receptors on mast cells triggers the release of preformed vasoactive mediators such as histamine, the synthesis of prostaglandins and leukotrienes, and, via a positive feedback loop, expression IL-4 and IL-13 [2].Its apparent association with airway diseases has recently focussed interest on the novel IL-7-like cytokine thymic stromal lymphopoietin (TSLP). TSLP expression is increased in asthmatic airways and correlates with both the expression of Th2-attracting chemokines and with disease severity [4-6], indicating a link between TSLP and human asthma. Furthermore it was shown that experimental lung-specific expression of TSLP leads to transgene-induced allergic airway inflammation characterized by a massive infiltration of leukocytes, goblet cell hyperplasia, and subepithelial fibrosis, as well as by increased serum IgE levels [7].TSLP is a typical four-helix-bundle cytokine 140 amino acid residues in length and was first cloned in humans in 2001 [8-10]. The human TSLP gene is localized on chromosome 5q22, interestingly close to the gene cluster encoding several Th2-related cytokines such as IL-4, IL-5, IL-9, and IL-13 [7,11]. Human TSLP is produced by different cell types in atopic asthma, mainly by epithelial and s