Multi-layered immune regulatory networks in cotton against Verticillium wilt

Cotton ( Gossypium spp.), a globally important economic crop, is severely threatened by Verticillium wilt caused by Verticillium dahliae ( V. dahliae ). This disease affects more than 40% of cotton fields in China and causes annual economic losses of 2.5-3.1 billion US dollars. Therefore, disease resistance breeding must take into account the inherent fitness trade-offs between disease resistance and fibre yield-quality performance. This review proposes that transcriptional regulation driven by cotton endogenous factors represents the central tier of the immune network underlying cotton resistance to Verticillium wilt. On this basis, epigenetic modifications and post-translational modifications (PTMs), which are co-orchestrated by the cotton host and pathogen effectors, act synergistically to shape a multi-layered immune regulatory architecture. At the transcriptional level, we systematically elaborate cotton endogenous core defense pathways mediated by Ca²⁺ signaling, reactive oxygen species (ROS) homeostasis, accumulation of antifungal metabolites, pathogenesis-related (PR) proteins, and their intricate crosstalk among phytohormone signaling pathways that coordinate defense responses. At the epigenetic level, we highlight the regulatory functions of DNA methylation, histone modification, chromatin remodeling, and ncRNAs during the interaction between cotton plants and V. dahliae . In particular, histone acetylation remodels chromatin status to regulate the transcriptional levels of TFs. At the PTM level, we summarize how phosphorylation, ubiquitination and SUMOylation dynamically regulate protein activity and stability to fine-tune the interaction between cotton and V. dahliae . Finally, we discuss emerging strategies for enhancing cotton resistance to Verticillium wilt, including AI-assisted multi-omics integration, CRISPR-based genome editing, structure-guided protein engineering, rhizosphere microbiome manipulation, and bionanotechnology applications. This review provides a framework for understanding cotton- V. dahliae interactions and offers valuable insight for the molecular breeding of disease-resistant cotton cultivars.