SABITA Research Highlights | September 2026

Ferroptosis and Immunity: Exploring the Role of Iron-Dependent Cell Death in Disease

What happens when a form of cell death driven by iron and oxidative stress begins to influence the immune system?

A review published in Clinical and Experimental Medicine explores the complex relationship between ferroptosis and immunity, highlighting how this regulated form of cell death may shape immune responses across a wide range of diseases.

Unlike apoptosis, ferroptosis is characterized by iron-dependent lipid peroxidation, a process in which oxidative damage accumulates in cell membranes. Its regulation involves interconnected pathways controlling iron metabolism, lipid metabolism, amino acid availability, and antioxidant defenses, particularly the glutathione–GPX4 system.

The review brings together evidence showing that immune cells respond differently to ferroptosis. Neutrophils, macrophages, dendritic cells, natural killer cells, and T and B lymphocytes exhibit distinct vulnerabilities depending on their metabolic requirements and antioxidant capacity. These differences can influence immune cell survival, inflammatory activity, antigen presentation, and the body’s ability to respond to infections and tumors.

One of the central insights is the dual role of ferroptosis in cancer immunity. While inducing ferroptosis in tumor cells may support anti-cancer strategies, ferroptosis in immune cells can weaken protective responses. For example, excessive lipid oxidation may impair the functions of cytotoxic T cells and natural killer cells, potentially limiting their ability to recognize and eliminate cancer cells.

Beyond cancer, the review examines evidence linking ferroptosis to autoimmune disorders, including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease. It also discusses its potential involvement in allergic reactions, infectious diseases, and tissue damage associated with inflammation.

These findings point toward an important challenge for future therapeutic development: targeting ferroptosis selectively. Rather than simply activating or inhibiting this cell death pathway, potential interventions may need to account for the specific immune cell types and disease environments involved.

By connecting molecular mechanisms with findings across immune-related diseases, the review provides a broader framework for understanding ferroptosis as a regulator of immunity and an emerging area of investigation for targeted therapeutic approaches. Further experimental and clinical research will be essential to establish how these mechanisms can be safely and effectively translated into treatments.

SABITA Researcher:  Mazdak Ganjalikhani Hakemi

*This study was conducted in collaboration with researchers from national partner institutions.

https://link.springer.com/article/10.1007/s10238-026-02321-1