Thymic stromal lymphopoietin (TSLP) is a Th2 alarmin that has been recently proposed as a master regulator in the pathogenesis of asthma, with elevated expression in asthmatic airways correlating with increased Th2 response and disease severity. Evidence suggests that dendritic cells (DCs) exposed to tissue TSLP are critical factors to drive a Th2 inflammatory response in the context of chronic asthma. Based on this, we set out to investigate the immunomodulatory effects of the PDE4 inhibitor tanimilast on TSLP-stimulated DCs to provide preliminary in vitro evidence for its therapeutic potential in asthma. Human primary CD1c+ DCs obtained from healthy subjects were used as a suitable model of DC fully responsive to TSLP, as indicated by a robust production of the Th2-recruiting chemokine CCL17, by the upregulation of the Th2-inducing molecule OX40L and by the capability to stimulate allogeneic naïve CD4+ T cell proliferation and Th2 polarization. When activated with TSLP in the presence of tanimilast, DCs retained the capability to stimulate T cell proliferation and Th2 polarization. However, Th2 effector cells differentiated in the presence of tanimilast displayed some functional features of the previously described ?regulatory Th2 cells? (Ito et al., J Exp Med. 2005; 202:1213-23). We are now in the process of dissecting the nature of tanimilast-induced Th2 cells phenotype in order to determine if they possess regulatory and anti-inflammatory properties potentially contributing to the restoration of homeostasis in the affected lung.