Differential regulation of cutaneous immunity by sensory neuron subsets

The nervous and immune systems have classically been studied as separate entities, but there is now mounting evidence for bidirectional communication between them in various organs, including the skin. The skin is an epithelial tissue with important sensory and immune functions. The skin is highly innervated with specialized subclasses of primary sensory neurons (PSNs) that can be in contact with skin-resident innate and adaptive immune cells. Neuroimmune crosstalk in the skin, through interactions of PSNs with the immune system, has been shown to regulate host cutaneous defense, inflammation, and tissue repair. Here, we review current knowledge about the cellular and molecular mechanisms involved in this crosstalk, as depicted via mouse model studies. We highlight the ways in which different immune challenges engage specialized subsets of PSNs to produce mediators acting on immune cell subsets and modulating their function.