PURPOSE: This present study aims to investigate the phenotype of IL-17A-producing T cells in thyroid-associated ophthalmopathy (TAO) and the role of IL-17A on RANTES and IL-16 expression in orbital fibroblasts (OFs) from TAO patients. METHODS: Blood samples were obtained from TAO patients and healthy controls and were subjected to ELISA and flow cytometry analysis. Primary human OFs cultured from surgical wastes were stimulated with IL-17A in the presence or absence of CD40L and were examined by qRT-PCR, ELISA, Western blotting, and apoptosis assays. RESULTS: We reported upregulated IL-17A, IFN-γ, RANTES, and IL-16 serum levels and increased frequency of IL-17A- and IFN-γ-producing T cells in peripheral blood mononuclear cells from patients with TAO compared with healthy controls. In addition, TAO orbital tissues were rich in T lymphocytes, expressing more IL-17A, IFN-γ, RANTES, and IL-16. Moreover, IL-17A could enhance the expression of RANTES, but not IL-16, in cultured primary OFs in cooperation with CD40L. We further validated that MAPK signaling was largely responsible for RANTES production in IL-17A-treated OFs. Finally, we demonstrated that IL-17A could not promote apparent apoptosis in OFs from TAO patients and healthy controls. CONCLUSIONS: Our results indicate the potent effect of IL-17A-induced RANTES expression on OFs and elaborate a possible mechanism in understanding Th17 cells in the pathology of TAO and its potential as a target to immunotherapy of TAO and other autoimmune disorders.
PURPOSE: This present study aims to investigate the phenotype of IL-17A-producing T cells in thyroid-associated ophthalmopathy (TAO) and the role of IL-17A on RANTES and IL-16 expression in orbital fibroblasts (OFs) from TAO patients. METHODS: Blood samples were obtained from TAO patients and healthy controls and were subjected to ELISA and flow cytometry analysis. Primary human OFs cultured from surgical wastes were stimulated with IL-17A in the presence or absence of CD40L and were examined by qRT-PCR, ELISA, Western blotting, and apoptosis assays. RESULTS: We reported upregulated IL-17A, IFN-γ, RANTES, and IL-16 serum levels and increased frequency of IL-17A- and IFN-γ-producing T cells in peripheral blood mononuclear cells from patients with TAO compared with healthy controls. In addition, TAO orbital tissues were rich in T lymphocytes, expressing more IL-17A, IFN-γ, RANTES, and IL-16. Moreover, IL-17A could enhance the expression of RANTES, but not IL-16, in cultured primary OFs in cooperation with CD40L. We further validated that MAPK signaling was largely responsible for RANTES production in IL-17A-treated OFs. Finally, we demonstrated that IL-17A could not promote apparent apoptosis in OFs from TAO patients and healthy controls. CONCLUSIONS: Our results indicate the potent effect of IL-17A-induced RANTES expression on OFs and elaborate a possible mechanism in understanding Th17 cells in the pathology of TAO and its potential as a target to immunotherapy of TAO and other autoimmune disorders.
Authors: Vardaan Gupta; Christine L Hammond; Elisa Roztocil; Mithra O Gonzalez; Steven E Feldon; Collynn F Woeller Journal: Surv Ophthalmol Date: 2021-09-04 Impact factor: 6.197
Authors: J Zhao; B Lin; H Deng; X Zhi; Y Li; Y Liu; P W Bible; Q Li; B Xu; L Wei; H Yang; D Huang Journal: Curr Mol Med Date: 2018 Impact factor: 2.222