Sphingolipid Metabolism in the Pathogenesis of Hashimoto’s Thyroiditis

TL;DR

This paper reviews how sphingolipid metabolism, especially the S1P signaling pathway, contributes to the development of Hashimoto’s thyroiditis and its link to thyroid cancer.

Contribution

The paper highlights SPL metabolism as a novel mechanistic link between autoimmunity, fibrosis, and carcinogenesis in Hashimoto’s thyroiditis.

Findings

Dysregulated SPHK/S1P/S1PR pathway is linked to immune polarization and chronic inflammation in HT.

S1P signaling promotes fibrosis and creates a pro-tumorigenic environment in HT.

SPL metabolism connects autoimmunity and cancer in Hashimoto’s thyroiditis.

Abstract

Hashimoto’s thyroiditis (HT) is the most common autoimmune thyroid disorder, characterized by progressive lymphocytic infiltration, follicular destruction, tissue fibrosis, and an elevated risk of thyroid carcinoma. While the precise mechanisms underlying HT remain incompletely defined, emerging evidence implicates dysregulated sphingolipid (SPL) metabolism, particularly the sphingosine-1-phosphate (S1P) signaling axis, as a central contributor to disease pathogenesis. S1P, a bioactive lipid mediator, integrates metabolic and immunological cues to regulate immune cell trafficking, cytokine production, apoptosis, and fibroblast activation. Aberrant activation of the sphingosine kinase (SPHK)/sphingosine-1-phosphate (S1P)/S1P receptor (S1PR) pathway has been linked to persistent T helper 1 (Th1) cell recruitment, signal transducer and activator of transcription 3 (STAT3)-mediated immune polarization, epithelial–mesenchymal transition, extracellular matrix remodeling, and the establishment of a chronic inflammatory and fibrotic microenvironment. Moreover, S1P signaling may foster a pro-tumorigenic niche, providing a mechanistic explanation for the strong epidemiological association between HT and papillary thyroid carcinoma. This review summarizes current insights into the role of SPL metabolism in HT, highlighting its potential as a mechanistic link between autoimmunity, fibrosis, and carcinogenesis.

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