Nikhil Dhingra1, Avner Shemer2, Joel Correa da Rosa3, Mariya Rozenblit4, Judilyn Fuentes-Duculan5, Julia K Gittler6, Robert Finney7, Tali Czarnowicki8, Xiuzhong Zheng5, Hui Xu5, Yeriel D Estrada9, Irma Cardinale5, Mayte Suárez-Fariñas8, James G Krueger8, Emma Guttman-Yassky10. 1. Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY; Columbia University College of Physicians & Surgeons, New York, NY. 2. Department of Dermatology, Tel-Hashomer, Tel Aviv, Israel. 3. Center for Clinical and Translational Science, The Rockefeller University, New York, NY. 4. Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; Center for Clinical and Translational Science, The Rockefeller University, New York, NY. 5. Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY. 6. Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY; Department of Dermatology, New York University School of Medicine, New York, NY. 7. Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY; Department of Dermatology, Jefferson Medical College, Philadelphia, Pa. 8. Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY; Center for Clinical and Translational Science, The Rockefeller University, New York, NY. 9. Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY. 10. Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address: eguttman@rockefeller.edu.
Abstract
BACKGROUND: Allergic contact dermatitis (ACD) is the most common occupational disease. Although murine contact hypersensitivity provides a framework for understanding ACD, it carries important differences from its human counterpart. Unlike the contact hypersensitivity model, which is induced by potent sensitizers (ie, dinitrofluorobenzene), human ACD is induced by weak-to-moderate sensitizers (ie, nickel), which cannot induce reactions in mice. Distinct hapten-specific immune-polarizing responses to potent inducers were suggested in mice, with unclear relevance to human ACD. OBJECTIVE: We explored the possibility of distinct T-cell polarization responses in skin to common clinically relevant ACD allergens. METHODS: Gene-expression and cellular studies were performed on common allergens (ie, nickel, fragrance, and rubber) compared with petrolatum-occluded skin, using RT-PCR, gene arrays, and immunohistochemistry. RESULTS: Despite similar clinical reactions in all allergen groups, distinct immune polarizations characterized different allergens. Although the common ACD transcriptome consisted of 149 differentially expressed genes across all allergens versus petrolatum, a much larger gene set was uniquely altered by individual allergens. Nickel demonstrated the highest immune activation, with potent inductions of innate immunity, TH1/TH17 and a TH22 component. Fragrance, and to a lesser extent rubber, demonstrated a strong TH2 bias, some TH22 polarization, and smaller TH1/TH17 contributions. CONCLUSIONS: Our study offers new insights into the pathogenesis of ACD, expanding the understanding of T-cell activation and associated cytokines in allergen-reactive tissues. It is the first study that defines the common transcriptome of clinically relevant sensitizers in human skin and identifies unique pathways preferentially activated by different allergens, suggesting that ACD cannot be considered a single entity.
BACKGROUND: Allergic contact dermatitis (ACD) is the most common occupational disease. Although murine contact hypersensitivity provides a framework for understanding ACD, it carries important differences from its human counterpart. Unlike the contact hypersensitivity model, which is induced by potent sensitizers (ie, dinitrofluorobenzene), human ACD is induced by weak-to-moderate sensitizers (ie, nickel), which cannot induce reactions in mice. Distinct hapten-specific immune-polarizing responses to potent inducers were suggested in mice, with unclear relevance to human ACD. OBJECTIVE: We explored the possibility of distinct T-cell polarization responses in skin to common clinically relevant ACD allergens. METHODS: Gene-expression and cellular studies were performed on common allergens (ie, nickel, fragrance, and rubber) compared with petrolatum-occluded skin, using RT-PCR, gene arrays, and immunohistochemistry. RESULTS: Despite similar clinical reactions in all allergen groups, distinct immune polarizations characterized different allergens. Although the common ACD transcriptome consisted of 149 differentially expressed genes across all allergens versus petrolatum, a much larger gene set was uniquely altered by individual allergens. Nickel demonstrated the highest immune activation, with potent inductions of innate immunity, TH1/TH17 and a TH22 component. Fragrance, and to a lesser extent rubber, demonstrated a strong TH2 bias, some TH22 polarization, and smaller TH1/TH17 contributions. CONCLUSIONS: Our study offers new insights into the pathogenesis of ACD, expanding the understanding of T-cell activation and associated cytokines in allergen-reactive tissues. It is the first study that defines the common transcriptome of clinically relevant sensitizers in human skin and identifies unique pathways preferentially activated by different allergens, suggesting that ACD cannot be considered a single entity.
Authors: Hitokazu Esaki; David A Ewald; Benjamin Ungar; Mariya Rozenblit; Xiuzhong Zheng; Hui Xu; Yeriel D Estrada; Xiangyu Peng; Hiroshi Mitsui; Thomas Litman; Mayte Suárez-Fariñas; James G Krueger; Emma Guttman-Yassky Journal: J Allergy Clin Immunol Date: 2015-01 Impact factor: 10.793
Authors: Boyi Liu; Yan Tai; Satyanarayana Achanta; Melanie M Kaelberer; Ana I Caceres; Xiaomei Shao; Jianqiao Fang; Sven-Eric Jordt Journal: Proc Natl Acad Sci U S A Date: 2016-11-07 Impact factor: 11.205
Authors: Lisa J Martin; Hua He; Margaret H Collins; J Pablo Abonia; Joceyln M Biagini Myers; Michael Eby; Hanna Johansson; Leah C Kottyan; Gurjit K Khurana Hershey; Marc E Rothenberg Journal: J Allergy Clin Immunol Date: 2017-11-10 Impact factor: 10.793