The Regulation of Immunological Processes by Peripheral Neurons in Homeostasis and Disease

The nervous system and the immune system are the principal sensory interfaces between the internal and external environment. They are responsible for recognizing, integrating, and responding to varied stimuli, and have the capacity to form memories of these encounters leading to learned or ‘adaptive’ future responses. We review current understanding of the cross-regulation between these systems. The autonomic and somatosensory nervous systems regulate both the development and deployment of immune cells, with broad functions that impact on hematopoiesis as well as on priming, migration, and cytokine production. In turn, specific immune cell subsets contribute to homeostatic neural circuits such as those controlling metabolism, hypertension, and the inflammatory reflex. We examine the contribution of the somatosensory system to autoimmune, autoinflammatory, allergic, and infectious processes in barrier tissues and, in this context, discuss opportunities for therapeutic manipulation of neuro-immune interactions.

TrendsHomeostasis: macrophages have been identified as key components of neurally-mediated circuits in various tissues including the gut, where they contribute to motility, and in adipose tissue, where they aid in thermogenesis.Barrier tissues: dendritic cells are found in close proximity to sensory neurons in the skin, gut, and lung, and the evidence suggests that they integrate signals from distinct neuronal subsets with either pro- or anti-inflammatory outcomes.Infection: pain during some cutaneous bacterial infections can be a direct result of bacterial products acting on sensory neurons rather than secondary to inflammatory processes.Subsets: an enhanced molecular understanding of neural and immune cell ontogeny and function has led to the generation of tools for ablation or functional modulation of specific cell subsets.