High-dimensionality approaches to the understanding and therapeutic manipulation of autoimmunity

Autoimmune disease may arise from disruptions in immune architecture rather than isolated molecular defects. High-dimensional immunology now reveals dynamic cellular states, regulatory circuits, and tissue-specific immune niches, but translation into therapy remains limited. We propose an Architecture-Anomaly-Target-Lead framework that contextualises therapeutic targets within immune organisation and complements Reset-Rebuild strategies. Together, these concepts provide a framework for developing and evaluating more sustained, tolerance-focused treatment approaches for autoimmune disease.