부산대학교 도서관

TSP‐1 is expressed by DCs and regulates secondary responses of allergic T cells in a mouse model of AED. Allergic eye disease, as in most forms of atopy, ranges in severity among individuals from immediate hypersensitivity to a severe and debilitating chronic disease. Dendritic cells play a key role in stimulating pathogenic T cells in allergen re‐exposure, or secondary responses. However, molecular cues by dendritic cells underpinning allergic T cell response levels and the impact that this control has on consequent severity of allergic disease are poorly understood. Here, we show that a deficiency in thrombospondin‐1, a matricellular protein known to affect immune function, has subsequent effects on downstream T cell responses during allergy, as revealed in an established mouse model of allergic eye disease. More specifically, we demonstrate that a thrombospondin‐1 deficiency specific to dendritic cells leads to heightened secondary T cell responses and consequent clinical disease. Interestingly, whereas thrombospondin‐1‐deficient dendritic cells augmented activity of allergen‐primed T cells, this increase was not recapitulated with naïve T cells in vitro. The role of dendritic cell‐derived thrombospondin‐1 in regulating secondary allergic T cell responses was confirmed in vivo, as local transfer of thrombospondin‐1‐sufficient dendritic cells to the ocular mucosa of thrombospondin‐1 null hosts prevented the development of augmented secondary T cell responses and heightened allergic eye disease clinical responses. Finally, we demonstrate that topical instillation of thrombospondin‐1‐derived peptide reduces T cell activity and clinical progression of allergic eye disease. Taken together, this study reveals an important modulatory role of dendritic cell‐derived thrombospondin‐1 on secondary allergic T cell responses and suggests the possible dysregulation of dendritic cell‐derived thrombospondin‐1 expression as a factor in allergic eye disease severity.