# Hypoxia-Inducible Factor 1-α in Autoimmune Diseases—Insights from the Paradigm of Hashimoto’s Thyroiditis: A Narrative Review

## TL;DR

This review explores how hypoxia-inducible factor 1-alpha (HIF-1α) contributes to Hashimoto’s thyroiditis, an autoimmune disease, and suggests it as a potential therapeutic target.

## Contribution

The paper highlights HIF-1α's role in Hashimoto’s thyroiditis and proposes it as a novel therapeutic target.

## Key findings

- HIF-1α stabilization in Hashimoto’s thyroiditis shifts T cell balance toward Th17 and away from regulatory T cells.
- Elevated mTOR/HIF-1α and reduced SIRT1 in T cells from HT patients support metabolic skewing.
- HIF-1α inhibitors or SIRT1 restorers may complement existing HT treatments.

## Abstract

Background/Objectives: Given the rising prevalence of autoimmune diseases and the need for new insights into the pathology of these disorders, it is important to summarize current knowledge, with an emphasis on Hashimoto’s thyroiditis (HT), since it is especially on the rise. Hypoxia is part of various pathophysiological conditions, and hypoxia-inducible factor (HIF) is a key factor in these processes. Hypoxia is involved in the regulation of hormones and the development of endocrine disorders. With this in mind, this narrative review summarizes the current state of knowledge on the relationship between autoimmune diseases, focusing on HT and the effects of hypoxia through the role of HIF. Methods: Multiple databases such as PubMed, NIH, Scopus, Web of Science, ScienceDirect, and Google Scholar were thoroughly searched for relevant keyword. Results: In HT, thyrocyte-derived reactive oxygen species and chronic lymphocytic infiltration stabilize HIF-1α, tilting CD4+ T cell polarity towards Th17 and away from regulatory T cells. Increased levels of Mammalian target of rapamycin (mTOR)/HIF-1α and reduced Sirtuin 1 (SIRT1) in T cells from patients diagnosed with HT confirm this metabolic skew. Furthermore, the data position HIF-1α as a therapeutic target. Inhibitors of mTOR or agents that restore SIRT1 could complement levothyroxine and antioxidant strategies. Hypoxia and the HIF signaling pathway have a role in energy homeostasis through various ways, for example, via metabolic effects of thyroid hormones, which are associated with the clinical manifestations of HT. Conclusions: Elucidation of HIF-1α-centered gene networks and testing of HIF-targeted interventions may curb the growing clinical burden of HT.