201. Transcriptome profiling reveals Th2 bias and identifies endogenous itch mediators in poison ivy contact dermatitis
- Author
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Boyi Liu, Chengyu Yin, Yan Tai, Ana Isabel Caceres, Sven-Eric Jordt, and Boyu Liu
- Subjects
Male ,0301 basic medicine ,Thymic stromal lymphopoietin ,medicine.medical_treatment ,Immunology ,Catechols ,medicine.disease_cause ,Oxazolone ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Th2 Cells ,0302 clinical medicine ,Allergen ,Thymic Stromal Lymphopoietin ,medicine ,Animals ,Humans ,Dermatitis, Toxicodendron ,Allergic contact dermatitis ,Skin ,Pharmacology ,business.industry ,Gene Expression Profiling ,Pruritus ,General Medicine ,Allergens ,Toxicodendron ,medicine.disease ,3. Good health ,Disease Models, Animal ,030104 developmental biology ,Cytokine ,chemistry ,030220 oncology & carcinogenesis ,Cytokines ,Antihistamine ,Inflammation Mediators ,business ,Contact dermatitis ,Histamine ,Signal Transduction ,Research Article ,Neuroscience - 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., Characterization of the immune and pruritic pathways in a mouse model of poison ivy-induced allergic contact dermatitis.
- Published
- 2019