From loci to mechanisms: wheat autoimmunity as a window into plant immune activation

Wheat (Triticum aestivum L.) is a major staple crop, and developing broad-spectrum resistance to multiple fungal pathogens is essential for sustainable production. Wheat autoimmunity (WAI) mutants represent genetic resources that spontaneously activate immune responses under non-stress conditions, exhibiting lesion-mimic or leaf-tip necrosis phenotypes and enhanced resistance to multiple foliar diseases, including powdery mildew and rusts. Increasing evidence indicates that WAI arises from dysregulation of immune homeostasis across multiple regulatory levels, involving receptor activation, cellular homeostasis, and membrane transport processes, ultimately converging on evolutionarily conserved defense outputs such as reactive oxygen species (ROS) accumulation, activation of defense-related genes, ion fluxes, and programmed cell death (PCD). Recent advances have identified key WAI-associated loci, including nucleotide-binding and leucine-rich-repeat receptors (NLRs), membrane proteins, regulatory components, and transporters, revealing mechanistically distinct pathways underlying constitutive immunity and its trade-off with growth. This review summarizes recent progress in the genetics and molecular mechanisms of WAI, critically assesses its roles in broad-spectrum, multi-disease resistance, and discusses strategies to minimize the growth and fitness costs. Furthermore, we propose that structure-guided allele optimization combined with spatiotemporal regulation of gene expression holds promise for the rational engineering of WAI alleles that confer durable disease resistance while minimizing associated fitness costs.