Interactions between skin-resident dendritic and Langerhans cells and pain-sensing neurons.

Various immune cells in the skin contribute to its function as a first line of defence against infection/disease, while its dense innervation by pain-sensing sensory neurons protects the host from injury/damage signals. Dendritic cells (DCs) are a heterogeneous population of cells that link the innate immune response to the adaptive response by capturing, processing, and presenting antigens to promote T-cell differentiation and activation. DCs are abundant across peripheral tissues, including the skin, where they are found in the dermis and epidermis. Langerhans cells (LCs) are a DC subset only located in the epidermis; both populations of cells can migrate to lymph nodes to contribute to broad immune responses. Dermal dendritic cells (DDCs) and LCs are found in close apposition with sensory nerve fibers in the skin and express neurotransmitter receptors, allowing them to communicate directly with the peripheral nervous system. Thus, neuroimmune signalling between DCs/LCs and sensory neurons can modulate physiological and pathophysiological pathways, including immune cell regulation, host defence, allergic response, homeostasis, and wound repair. Here, we summarize the latest discoveries on DC- and LC-neuron interaction with neurons while providing an overview of gaps and areas not previously explored. Understanding the interactions between these two systems may provide key insight into developing therapeutic targets for treating diseases such as psoriasis, neuropathic pain, and lupus.