Chemokine-mediated Treg trafficking is required to suppress allergic airway inflammation (175.12)

Abstract

Abstract Research has implicated a role for regulatory T cells (Tregs) in preventing asthma; however, where Tregs exert their regulatory function and the mechanisms that localize Tregs to their functional location have not been addressed. We hypothesized that chemokine receptors expressed on Tregs play an important role in directing these cells to the allergic lung and/or the reactive lymph node. We developed two murine models of allergic airway to address this hypothesis. In the sensitization model, naïve mice are injected with antigen-specific Tregs prior to immunization and aerosol challenge. In the effector model, antigen-specific Tregs are injected into mice after immunization but prior to aerosol antigen challenge. Transferred wildtype Tregs are capable of suppressing allergic airway inflammation in both models. We have found that CCR7 is required in the sensitization model and CCR4 is required in the effector model, suggesting Treg trafficking into lymph nodes is required to suppress allergic airway inflammation during the allergen sensitization phase while Treg trafficking into the lung is required to suppress allergic airway inflammation during the recall response to allergen. Using a segmental allergen challenge model in human allergic asthma subjects we further show an important role for CCR4+ Tregs in human allergic asthma. These results support our mouse data and demonstrate that CCR4 may play an important role in Treg recruitment into the allergic airways of humans.