Intervention of thymus and activation-regulated chemokine attenuates the development of allergic airway inflammation and hyperresponsiveness in mice

Thymus- and activation-regulated chemokine (TARC; CCL17) is a lymphocyte-di rected CC chemokine that specifically chemoattracts CC chemokine receptor 4 -positive (CCR4(+)) Th2 cells. To establish the pathophysiological roles of TARC in vivo, we investigated here whether an mAb against TARC could inhib it the induction of asthmatic reaction in mice elicited by OVA, TARC was co nstitutively expressed in the lung and was up-regulated in allergic inflamm ation. The specific Ab against TARC attenuated OVA-induced airway eosinophi lia and diminished the degree of airway hyperresponsiveness with a concomit ant decrease in Th2 cytokine levels. Our results for the first time indicat e that TARC is a pivotal chemokine for the development of Th2-dominated exp erimental allergen-induced asthma with eosinophilia and AHR. This study als o represents the first success in controlling Th2 cytokine production in vi vo by targeting a chemokine.