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Review
. 2023 Apr 4:14:1170884.
doi: 10.3389/fendo.2023.1170884. eCollection 2023.

Sphingolipids in thyroid eye disease

Anne Gulbins  1 , Gina-Eva Görtz  1 , Erich Gulbins  2 , Anja Eckstein  1
Affiliations
Review

Sphingolipids in thyroid eye disease

Anne Gulbins et al. Front Endocrinol (Lausanne). .

Abstract

Graves' disease (GD) is caused by an autoimmune formation of autoantibodies and autoreactive T-cells against the thyroid stimulating hormone receptor (TSHR). The autoimmune reaction does not only lead to overstimulation of the thyroid gland, but very often also to an immune reaction against antigens within the orbital tissue leading to thyroid eye disease, which is characterized by activation of orbital fibroblasts, orbital generation of adipocytes and myofibroblasts and increased hyaluronan production in the orbit. Thyroid eye disease is the most common extra-thyroidal manifestation of the autoimmune Graves' disease. Several studies indicate an important role of sphingolipids, in particular the acid sphingomyelinase/ceramide system and sphingosine 1-phosphate in thyroid eye disease. Here, we discuss how the biophysical properties of sphingolipids contribute to cell signaling, in particular in the context of thyroid eye disease. We further review the role of the acid sphingomyelinase/ceramide system in autoimmune diseases and its function in T lymphocytes to provide some novel hypotheses for the pathogenesis of thyroid eye disease and potentially allowing the development of novel treatments.

Keywords: Graves’ disease; acid sphingomyelinase 2; ceramide; sphingolipids; thyroid eye disease (TED).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Summary of the main molecular mechanisms in thyroid eye disease (TED).
Figure 2
Figure 2
Schematic overview over the synthesis and consumption of ceramide, sphingomelin and sphingosine.
Figure 3
Figure 3
Possible function of sphingolipids in thyroid eye disease (TED).
See this image and copyright information in PMC

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