Integrated control of leukocyte compartments as a feature of adaptive physiology

As a highly diverse and mobile organ, the immune system is uniquely equipped to participate in tissue responses in a tunable manner, depending on the number, type, and nature of cells deployed to the respective organ. Most acute organismal stressors that threaten survival—predation, infection, poisoning, and others—induce pronounced redistribution of immune cells across tissue compartments. Here, we review the current understanding of leukocyte compartmentalization under homeostatic and noxious conditions. We argue that leukocyte shuttling between compartments is a function of local tissue demands, which are linked to the organ’s contribution to adaptive physiology at steady state and upon challenge. We highlight the neuroendocrine signals that relay and organize this trafficking behavior and outline mechanisms underlying the functional diversification of leukocyte responses. In this context, we discuss important areas of future inquiry and the implications of this scientific space for clinical medicine in the era of targeted immunomodulation.