Neural Regulation of Skin Immunity

The exploration of neuroimmune interactions at tissue barriers has become pivotal for our understanding of how organisms survive and adapt to challenging environments. Serving both as a physical barrier and a sensory organ, the skin has evolved as a key interface where sensation and immunity dynamically converge. In this review, we first explore the microanatomy of the skin neuroimmune system. We then discuss current knowledge on the local regulation of skin immunity by sensory neurons in steady state, injury, and infection. We highlight key pathways involved in resistance to environmental insults and discuss how their dysregulation contributes to skin physiopathology. Our emphasis on the afferent neuronal wiring connecting the skin and the brain is followed by a detailed examination of the spinal and brain efferent pathways, including neuroendocrine and cognitive circuits, that remotely modulate skin immunity. By integrating cutting-edge insights from neurobiology, immunology, and skin biology, we present a holistic view of how the nervous system sustains homeostasis of the cutaneous barrier.