Regulation of Lymphocyte Function by PPAR: Relevance to Thyroid Eye Disease-Related Inflammation
Figure 1
According to one current model, TED is triggered by binding and activation of orbital fibroblasts by autoantibodies. These autoantibodies could be specific for antigens such as TSH-R and/or IGF-1R. Activated orbital fibroblasts release chemokines, including IL-16, RANTES, and CXCL10, which recruit T lymphocytes into the orbit. These lymphocytes then interact with fibroblasts, potentially activating each other, further promoting cytokine production (IFN, TNF,
PGD2, and 15d-PGJ2) and secretion of T cell-activating factors by the fibroblasts (IL-8 and CXCL10). Fibroblasts are also stimulated to secrete IL-6 (promoting B cell differentiation) and to increase autoantigen presentation, both of which amplify the overall response. The interactions of fibroblasts with T cells result in the deposition of extracellular matrix molecules, fibroblast proliferation, and fat accumulation.
