IL-31, which is a four-helix-bundle cytokine, is another important itch mediator for AD that functions by binding with heterodimer comprised of IL-31 receptor A (IL-31RA) and tumorigenic M. Moreover, IL-31RA is the key neuroimmune link between Th2 cells and sensory nerve; furthermore, high IL-31RA expression could cause pruritus by activating skin nerve endings (Otsuka et al., 2011; Sonkoly et al., 2006). The gene discussed is IL31; the disease is Alzheimer disease.