K Malik1,2, B Ungar1,2, S Garcet2, R Dutt1, D Dickstein1, X Zheng2, H Xu1, Y D Estrada1, M Suárez-Fariñas2,3,4,5, A Shemer6, J G Krueger2, E Guttman-Yassky1,2,4,7. 1. Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 2. Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA. 3. Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 4. Department of Genetics and Genomics Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 5. Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 6. The Department of Dermatology, Tel-Hashomer, Tel-Aviv, Israel. 7. The Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Abstract
BACKGROUND: House dust mite/HDM atopy patch test/APT elicits positive reactions in a high fraction of atopic dermatitis/AD and healthy individuals. Experimental systems for new-onset/chronic AD are needed to support rapid therapeutic development, particularly since animal models representing human AD are lacking. While HDM APT has been considered to simulate AD, its suitability to model AD's emerging Th2/Th22 phenotype with Th1 and Th17 components is unknown. OBJECTIVE: To assess whether HDM APT reproduces AD. METHODS: Positive HDM APTs (n = 15) from patients with and without AD were evaluated, using genomic and immunohistochemistry studies, against intrapersonal control skin. RESULTS: APT lesions showed higher T cell and dendritic cell infiltrates vs. CONTROLS: Seven hundred and forty-three up- and 326 downregulated genes were differentially expressed in HDM APT (fold change >2 and false discovery rate < 0.05), with increased expression of Th2, Th9, Th17/Th22 polar cytokines (i.e. IL-5, IL-13, IL-9, IL-17, IL-22). CONCLUSION: While HDM caused significant Th2 skewing, it also illustrated differences in Th2 induction and barrier defects; thus, HDM APT does not fully simulate AD. Given its widespread availability and sensitization rates, HDM may potentially be a useful tool that represents select aspects of AD, psoriasis, or contact dermatitis.
BACKGROUND: House dust mite/HDM atopy patch test/APT elicits positive reactions in a high fraction of atopic dermatitis/AD and healthy individuals. Experimental systems for new-onset/chronic AD are needed to support rapid therapeutic development, particularly since animal models representing humanAD are lacking. While HDM APT has been considered to simulate AD, its suitability to model AD's emerging Th2/Th22 phenotype with Th1 and Th17 components is unknown. OBJECTIVE: To assess whether HDM APT reproduces AD. METHODS: Positive HDM APTs (n = 15) from patients with and without AD were evaluated, using genomic and immunohistochemistry studies, against intrapersonal control skin. RESULTS: APT lesions showed higher T cell and dendritic cell infiltrates vs. CONTROLS: Seven hundred and forty-three up- and 326 downregulated genes were differentially expressed in HDM APT (fold change >2 and false discovery rate < 0.05), with increased expression of Th2, Th9, Th17/Th22 polar cytokines (i.e. IL-5, IL-13, IL-9, IL-17, IL-22). CONCLUSION: While HDM caused significant Th2 skewing, it also illustrated differences in Th2 induction and barrier defects; thus, HDM APT does not fully simulate AD. Given its widespread availability and sensitization rates, HDM may potentially be a useful tool that represents select aspects of AD, psoriasis, or contact dermatitis.
Authors: Carolyn M Walsh; Rose Z Hill; Jamie Schwendinger-Schreck; Jacques Deguine; Emily C Brock; Natalie Kucirek; Ziad Rifi; Jessica Wei; Karsten Gronert; Rachel B Brem; Gregory M Barton; Diana M Bautista Journal: Elife Date: 2019-10-21 Impact factor: 8.140
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