Orbital Fibroblasts Exhibit a Novel Pattern of Responses to Proinflammatory Cytokines: Potential Basis for the Pathogenesis of Thyroid-Associated Ophthalmopathy

Abstract

Thyroid-associated ophthalmopathy (TAO) represents a process confined to the orbit where the connective tissue becomes inflamed and accumulates the glycosaminoglycan, hyaluronan. Ultimately, the orbital tissues become extensively remodeled. Evidence points to the recruitment and activation of T cells as critical elements initiating and driving the pathogenesis of TAO. The phenotype of orbital fibroblasts appears to be distinct from that of other types of fibroblasts. These cells exhibit particularly robust responses to a number of T-cell–derived cytokines. Notable among these are the inductions of key inflammatory genes and their products. We hypothesize that exaggerated cellular responses represent the basis for the involvement of the orbit in Graves' disease.