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

Abstract

In the United States, poison ivy exposure is the most common naturally occurring allergen to cause 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 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 substance P, 5-HT, ET-1, but not TSLP or histamine. Injections of a TSLP monoclonal neutralizing antibody, 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 study. 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.

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  • Authors

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    Source

    JCI insight 5: 2019 Jun 11 pg

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31184997

    Citation

    Liu, Boyi, et al. "Transcriptome Profiling Reveals Th2 Bias and Identifies Endogenous Itch Mediators in Poison Ivy Contact Dermatitis." JCI Insight, vol. 5, 2019.
    Liu B, Tai Y, Liu B, et al. Transcriptome profiling reveals Th2 bias and identifies endogenous itch mediators in poison ivy contact dermatitis. JCI Insight. 2019;5.
    Liu, B., Tai, Y., Liu, B., Caceres, A. I., Yin, C., & Jordt, S. E. (2019). Transcriptome profiling reveals Th2 bias and identifies endogenous itch mediators in poison ivy contact dermatitis. JCI Insight, 5, doi:10.1172/jci.insight.124497.
    Liu B, et al. Transcriptome Profiling Reveals Th2 Bias and Identifies Endogenous Itch Mediators in Poison Ivy Contact Dermatitis. JCI Insight. 2019 Jun 11;5 PubMed PMID: 31184997.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Transcriptome profiling reveals Th2 bias and identifies endogenous itch mediators in poison ivy contact dermatitis. AU - Liu,Boyi, AU - Tai,Yan, AU - Liu,Boyu, AU - Caceres,Ana I, AU - Yin,Chengyu, AU - Jordt,Sven-Eric, Y1 - 2019/06/11/ PY - 2019/6/12/entrez PY - 2019/6/12/pubmed PY - 2019/6/12/medline KW - Cytokines KW - Immunology KW - Neuroscience KW - Pharmacology JF - JCI insight JO - JCI Insight VL - 5 N2 - In the United States, poison ivy exposure is the most common naturally occurring allergen to cause 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 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 substance P, 5-HT, ET-1, but not TSLP or histamine. Injections of a TSLP monoclonal neutralizing antibody, 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 study. 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. SN - 2379-3708 UR - https://www.unboundmedicine.com/medline/citation/31184997/Transcriptome_profiling_reveals_Th2_bias_and_identifies_endogenous_itch_mediators_in_poison_ivy_contact_dermatitis L2 - https://doi.org/10.1172/jci.insight.124497 DB - PRIME DP - Unbound Medicine ER -