Journal of agricultural and food chemistryOct 18, 2024

T-2 Toxin May Cause Aging of Immune Cells by Activating Low-Oxygen and DNA-Sensing Pathways in Macrophages

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 2, 2026

Abstract

T-2 toxin at 14 nM induces immunosenescence in RAW264.7 cells by activating the HIF-1α/cGAS-STING pathway.

T-2 toxin triggers an intracellular hypoxic environment that activates HIF-1α, which may protect cells under normal conditions.
Immunosenescence, associated with aging immune function, is potentially accelerated by T-2 toxin exposure.
The cGAS-STING pathway is involved in promoting cell senescence and apoptosis, but is negatively regulated by HIF-1α.
PARP 1 cleavage by caspase 3/9 may inhibit DNA repair, contributing to the transition from senescence to apoptosis.
At 12 hours of exposure, T-2 toxin disrupts the balance of cytoskeletal components, leading to cellular senescence.

Simplified

T-2 toxin induces cell immunotoxicity by triggering an intracellular hypoxic microenvironment and activates hypoxia-inducible factor-1α (HIF-1α), which exerts cellular protective effects. Mycotoxins can also induce senescence. The aging of immune function, termed "immunosenescence," is an important factor in the decline of biological immunity and accelerates senescence. However, the mechanism underlying T-2 toxin-induced immunosenescence remains unclear. This study aimed to elucidate the roles of HIF-1α and cGAS-STING signaling in this process and uncover the mechanisms through which T-2 toxin impacts cytoskeletal integrity and cellular senescence using a RAW264.7 macrophage model. The cells were treated with T-2 toxin (14 nM) for 1-24 h. We revealed that T-2 toxin-induced immunosenescence in RAW264.7 cells by activating the HIF-1α/cGAS-STING axis. The cGAS-STING pathway promotes cell senescence and apoptosis; however, we revealed that HIF-1α negatively regulated this pathway, thereby inhibiting cellular senescence and apoptosis. However, PARP 1 cleavage by caspase 3/9 inhibited DNA repair and accelerated the transition from senescence to apoptosis. At the late stages of T-2 toxin exposure (12 h), HIF-1α accelerated cellular senescence by disrupting the dynamic balance of cytoskeletal α-tubulin and F-actin and destabilizing the cytoskeletal structure. Our research demonstrates that T-2 toxin induces immunosenescence in RAW264.7 cells by activating the cGAS-STING pathway, with HIF-1α signaling serving as a negative regulator. This study provides a deeper understanding of T-2 toxin-induced immunosenescence.

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T-2 Toxin May Cause Aging of Immune Cells by Activating Low-Oxygen and DNA-Sensing Pathways in Macrophages

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