Molecular profiling of contact dermatitis skin identifies allergen-dependent differences in immune response

Nikhil Dhingra, Avner Shemer, Joel Correa Da Rosa, Mariya Rozenblit, Judilyn Fuentes-Duculan, Julia K. Gittler, Robert Finney, Tali Czarnowicki, Xiuzhong Zheng, Hui Xu, Yeriel D. Estrada, Irma Cardinale, Mayte Suárez-Fariñas, James G. Krueger, Emma Guttman-Yassky

Research output: Contribution to journalArticle

98 Scopus citations

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/T H17 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.

Original languageEnglish (US)
Pages (from-to)362-372
Number of pages11
JournalJournal of Allergy and Clinical Immunology
Volume134
Issue number2
DOIs
StatePublished - Aug 2014
Externally publishedYes

Keywords

  • Allergic contact dermatitis
  • T-cell polarization
  • allergens
  • fragrance
  • human skin
  • nickel
  • patch testing
  • rubber

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Dhingra, N., Shemer, A., Correa Da Rosa, J., Rozenblit, M., Fuentes-Duculan, J., Gittler, J. K., Finney, R., Czarnowicki, T., Zheng, X., Xu, H., Estrada, Y. D., Cardinale, I., Suárez-Fariñas, M., Krueger, J. G., & Guttman-Yassky, E. (2014). Molecular profiling of contact dermatitis skin identifies allergen-dependent differences in immune response. Journal of Allergy and Clinical Immunology, 134(2), 362-372. https://doi.org/10.1016/j.jaci.2014.03.009