Material-inspired paradigms in metalloimmunology: from fundamental insights to therapeutic intervention

Metalloimmunology, an emerging interdisciplinary field, is reshaping our understanding of the immune system at an unprecedented pace. This review systematically elaborates on the core roles of metal ions as critical signaling molecules and metabolic regulators in both innate and adaptive immunity. Special focus is placed on the molecular mechanisms by which metal ions modulate key immune signaling pathways, as well as their mediation of novel immunogenic cell death modalities including ferroptosis, cuproptosis, and pyroptosis. Furthermore, we comprehensively review innovative metal ion-based therapeutic strategies, encompassing metal nanoadjuvants, metal-organic frameworks and nanozymes, along with their cutting-edge applications in cancer, infectious diseases, autoimmune disorders, and tissue repair. Finally, this review delves into the challenges faced by this field in targeted delivery, biosafety, and clinical translation, and provides an outlook on its future development directions with particular emphasis on the immense potential of precisely regulating metal homeostasis for the treatment of autoimmune diseases.