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December 4, 2025Cell Death and Disease21 citationsOpen Access

Immune cells dying from ferroptosis: mechanisms and therapeutic opportunities

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BYBinhang YuanSZShengtao Zhou

Key Points

  • Ferroptosis influences the function of immune cells, particularly macrophages and natural killer cells, in regulating immune responses.
  • Macrophages and dendritic cells actively participate in ferroptosis pathways, contributing to inflammation and immune homeostasis.
  • Review of recent advances reveals therapeutic opportunities targeting small molecule inhibitors of ferroptosis in autoimmune diseases.
  • Involvement of epigenetic regulation by EZH2 connects ferroptosis and tumorigenesis in immune-related disorders.

Abstract

Abstract This review explores the intricate regulation of ferroptosis through diverse pathways and related metabolism, focusing on the mechanisms of ferroptosis in diverse immune cells, including granulocytes, macrophages, dendritic cells, T/B lymphocytes, natural killer/ innate lymphoid cells, under conditions of iron metabolism imbalance and lipid peroxidation accumulation, highlighting their pivotal roles in the dynamic regulation of immune microenvironments. Furthermore, the review summarizes the therapeutic potential of targeting ferroptosis pathways in tumor immunity, pathogen infections, inflammation, and autoimmune diseases. It systematically compiles recent advances in ferroptosis-related drugs and small molecule inhibitors, while proposing novel therapeutic strategies through intervention in ferroptosis-immune interactions for immune-related disorders. Additionally, this review summarizes the mechanisms of epigenetic regulation of ferroptosis. As a core enzyme in epigenetic regulation, Enhancer of zeste homolog 2 (EZH2) serves as a pivotal node linking epigenetic regulation, tumorigenesis, immune control, and ferroptosis, providing novel therapeutic insights for anti-tumor immunity.

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Cite This Study

Yuan et al. (2025) studied this question.

synapsesocial.com/papers/6930e8b6ea1aef094cca2f91https://doi.org/10.1038/s41419-025-08204-9
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