TNF-α, CCL-2 and CCL-20 play an important role in an autoimmune hyperthyroid mouse model

Introduction Graves' disease is an autoimmune disease mediated by autoantibodies against the TSH receptor. We developed and established an experimental GO mouse model by genetic immunization of BALB/c mice with a plasmid encoding the A-subunit of human TSHR. The retroorbital tissue shows a diffuse infiltration of immune cells in patients with GO. The aim of this work was to analyze the role of cytokines in our established mouse model.

Material and Methods 31 female BALB/c mice were immunized, 14 of them with the TSHR A-subunit plasmid and 17 with control β-Gal plasmid. Immunohistochemical studies of F4/80, CD3 and TNF-α were performed and the migration of macrophages was analyzed. In addition, cytokine analyses were performed using Legend Plex and ELISA.

Results The retroorbital tissue showed signs of inflammation with macrophages and CD3-positive T cells, and furthermore increased presence of TNF-α positive cells. In the migration test stimulation with TNF-α led to increased inflammation in the mouse orbita fibroblasts (mOF´s). Stimulation with TNF-α led furthermore to higher levels of CCL-2 and CCL-20 in TSHR-immunized mice.

Discussion The present study shows that TNF-α seems to play an important role in the pathophysiology of GO. TNF-α is elevated in this autoimmune hyperthyroid mouse model. In this work the cytokine spectrum in mOFs of GO mice and control mice was analyzed for the first time. CCL-2 and CCL-20 appear to be disease modulating chemokines for Grave's orbitopathy.

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Publication History

Article published online:
13 May 2021