Nature Immunology, Published online: 19 September 2025; doi:10.1038/s41590-025-02294-5

The artificial intelligence (AI)-designed peptide SK56 blocks mature gasdermin D pores, delaying pyroptosis and inflammatory cytokine release. This reduces dendritic cell hyperactivation and prevents the spread of pyroptosis to nearby cells. SK56 also protects against mitochondrial damage and improves survival in septic mice, demonstrating its potential as a new post-pyroptosis, anti-inflammatory therapy.



Summary

An AI-designed peptide, SK56, effectively blocks mature gasdermin D pores, mitigating the effects of pyroptosis, an inflammatory cell death pathway. By inhibiting pore formation, SK56 reduces inflammatory cytokine release and dendritic cell hyperactivation, preventing pyroptosis from spreading. Furthermore, SK56 protects against mitochondrial damage, a common consequence of pyroptosis. In a septic mouse model, SK56 improved survival rates, highlighting its potential as a novel anti-inflammatory therapeutic agent targeting post-pyroptosis events. This research suggests SK56 offers a promising strategy to manage inflammatory conditions associated with pyroptosis.

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