HIF-1α inhibits T-2 toxin-mediated "immune evasion" process by negatively regulating PD-1/PD-L1
Language English Country Ireland Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
36115646
DOI
10.1016/j.tox.2022.153324
PII: S0300-483X(22)00236-0
Knihovny.cz E-resources
- Keywords
- HIF-1α, Hypoxia, Immune evasion, PD-1/PD-L1, T-2 toxin,
- MeSH
- B7-H1 Antigen metabolism MeSH
- Programmed Cell Death 1 Receptor metabolism MeSH
- Hypoxia-Inducible Factor 1, alpha Subunit pharmacology MeSH
- Hypoxia MeSH
- Humans MeSH
- T-2 Toxin * toxicity MeSH
- Trichothecenes * toxicity MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- B7-H1 Antigen MeSH
- Programmed Cell Death 1 Receptor MeSH
- Hypoxia-Inducible Factor 1, alpha Subunit MeSH
- T-2 Toxin * MeSH
- Trichothecenes * MeSH
Trichothecene mycotoxins have a strong immunosuppressive effect, which may even escape host immune surveillance and damage the immune repair to show an "immune evasion" effect. Increasing lines of evidence have shown that hypoxia and hypoxia-inducible factors (HIFs) are key mediators of trichothecenes, and these toxins appear to be closely related to the "immune evasion" mechanisms. Therefore, we used RAW264.7 cell model to explore the association of T-2 toxins with "immune evasion" process and hypoxia, as well as their cross-linking effects induced by T-2 toxin. Our results showed that HIF-1α is an important toxicity target of T-2 toxin, which could induce intracellular hypoxia. T-2 toxin induced an "immune evasion" process by activating the PD-1/PD-L1 signaling pathway. Interestingly, when HIF-1α activation was blocked, the "immune evasion" process regulated by PD-1/PD-L1 signaling was activated, resulting in the cells damage, suggesting that hypoxia induced by T-2 toxin plays a protective role for RAW264.7 cell damage. Thus, our work shows that HIF-1α inhibits T-2 toxin-mediated "immune evasion" process by negatively regulating PD-1/PD-L1signaling. This study contributes to a better understanding of the immunotoxicity mechanism of trichothecenes.
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