Transcriptome profiling reveals Th2 bias and identifies endogenous itch mediators in poison ivy contact dermatitis

In the United States, poison ivy is the most common naturally occurring allergen that causes allergic contact dermatitis (ACD). The immune and pruritic mechanisms associated with poison ivy ACD remain largely unexplored. Here, we compared skin whole transcriptomes and itch mediator levels in mouse ACD models induced by the poison ivy allergen, urushiol, and the synthetic allergen, oxazolone. The urushiol model produced a Th2-biased immune response and scratching behavior, resembling findings in poison ivy ACD patients. Urushiol-challenged skin contained elevated levels of the cytokine thymic stromal lymphopoietin (TSLP), a T cell regulator and itch mediator, and pruritogenic serotonin (5-HT) and endothelin (ET-1) but not substance P (SP) or histamine. The oxazolone model generated a mixed Th1/Th2 response associated with increased levels of SP, 5-HT, and ET-1 but not TSLP or histamine. Injections of a TSLP monoclonal neutralizing antibody or serotonergic or endothelin inhibitors, but not SP inhibitors or antihistamines, reduced scratching behaviors in urushiol-challenged mice. Our findings suggest that the mouse urushiol model may serve as a translational model of human poison ivy ACD. Inhibiting signaling by TSLP and other cytokines may represent alternatives to the standard steroid/antihistamine regimen for steroid-resistant or -intolerant patients and in exaggerated systemic responses to poison ivy.