Markus Huber-Lang, Tianmeng Chen, Rebecca Halbgebauer, Timothy Billiar
Trauma disrupts the structure-function interplay of life, instantly engaging innate and adaptive immunity together with neuroendocrine, endovascular and metabolic axes. The immune response emerges from disturbances in overarching hallmarks of any living being-barrier systems, molecular communication and adaptation-further shaped by patient-specific, injury-specific and modern care-specific determinants. These factors drive adaptive or maladaptive immune trajectories, from restitution to chronic dysfunction or death. Multi-omics analyses of trauma cohorts now enable endotype discovery, providing a framework for mechanism-guided, spatiotemporal precision immunomodulation. This Review focuses exclusively on human studies to conceptualize major themes in clinical trauma immunology to guide future research.