Abstract
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.
Highlights
Allergic contact dermatitis (ACD) is a common skin condition resulting from cutaneous contact with an allergen [1]
None of the abovementioned endogenous itch mediators was increased in the plasma of the oxazolone group, whereas thymic stromal lymphopoietin (TSLP) was significantly increased in the plasma of the urushiol model (Figure 5B). These results identified substance P and TSLP as key, distinct endogenous itch mediators released in the inflamed skin or plasma of the oxazolone and urushiol models, respectively, implying that, in addition to the distinct immune responses, distinct pruritic mechanisms may be activated in these 2 models
SB, Ket, BQ123, L733060, and TSLP-neutralizing Ab at dosages used above did not affect the locomotor activity of the mice tested by rotarod assay (Figure 6F). These findings demonstrate that TSLP, 5-HT, and ET-1 signaling promote itch-related scratching behavior in the urushiol-induced ACD mouse model and that both common and distinct pruritogenic mechanisms are engaged in the oxazolone and urushiol models
Summary
Allergic contact dermatitis (ACD) is a common skin condition resulting from cutaneous contact with an allergen [1]. In the United States, the most common naturally occurring allergen-induced ACD is caused by contact with poison ivy and related plants, including poison sumac and poison oak [2, 3]. Elevated atmospheric CO2 levels and climate change have increased the biomass and geographic range of poison ivy and urushiol content, resulting in more toxic plants [6]. These effects will likely increase the incidence of poison ivy ACD in the future [7]
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