Search

Thymic stromal lymphopoietin (TSLP) is an epithelial-derived cytokine that has been implicated in the initiation of allergic responses. CD4 T cells and dendritic cells are able to respond to TSLP in vitro; however, there has not been a careful dissection of the spatiotemporal response to TSLP by CD4 T cells in vivo during an allergic response. Previous work has suggested a requirement for TSLP in amplifying Th2 responses during allergen challenge by direct action on CD4 T cells; however, these studies did not determine whether there is an effect of TSLP on CD4 T cells during allergen sensitization. In this study we demonstrate an indirect role for TSLP on CD4 T cells during sensitization and challenge phases of an allergic response. This indirect effect of TSLP on CD4 T cells is due in part to the presence of TSLP exclusively in the allergen-sensitized and -challenged skin, rather than the draining lymph nodes. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are critical in immune responses, linking innate and adaptive immunity. We found here that DC-specific deletion of the transcription factor STAT5 was not critical for development but was required for T helper type 2 (TH2), but not TH1, allergic responses in both the skin and lungs. Loss of STAT5 in DCs led to the inability to respond to thymic stromal lymphopoietin (TSLP). STAT5 was required for TSLP-dependent DC activation, including upregulation of the expression of costimulatory molecules and chemokine production. Furthermore, TH2 responses in mice with DC-specific loss of STAT5 resembled those seen in mice deficient in the receptor for TSLP. Our results show that the TSLP-STAT5 axis in DCs is a critical component for the promotion of type 2 immunity at barrier surfaces. [ABSTRACT FROM AUTHOR]