Transcriptional regulation of human dorsal root ganglia cultures by type 2 cytokines

Cutaneous afferent neurons express receptors for type 2 cytokines, including interleukins (IL)-4, IL-13, and IL-33. These neuronal cytokine receptors were found to be required in several murine models of itch. The objective of the present study was to determine if type 2 cytokine stimulation sensitizes sensory neurons to future itch stimuli in a fully human ex vivo system. Human dorsal root ganglia were isolated and dissociated to establish ex vivo cultures and subjected to 24 hours of type 2 cytokine exposure with either vehicle, IL-4, IL-13, IL-33, or IL-4 and IL-13 together. After 24 hours, cells were harvested and RNA extracted and sequenced to determine the transcriptomic effects of type 2 cytokine exposure. Cultures were stimulated with 500 nM IL-4, IL-13, IL-33 or the combination of IL-4 and IL-13 for 24 hours. Vehicle alone and a cocktail of inflammatory mediators "CIS" were as negative and positive controls.