Molecular profiling of contact dermatitis skin identifies allergen-dependent differences in immune response.
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.
Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY; Columbia University College of Physicians & Surgeons, New York, NY.
Nikhil
N
Dhingra
Department of Dermatology, Tel-Hashomer, Tel Aviv, Israel.
Avner
A
Shemer
Center for Clinical and Translational Science, The Rockefeller University, New York, NY.
Joel
J
Correa da Rosa
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.
Mariya
M
Rozenblit
Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY.
Judilyn
J
Fuentes-Duculan
Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY; Department of Dermatology, New York University School of Medicine, New York, NY.
Julia K
JK
Gittler
Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY; Department of Dermatology, Jefferson Medical College, Philadelphia, Pa.
Robert
R
Finney
Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY; Center for Clinical and Translational Science, The Rockefeller University, New York, NY.
Tali
T
Czarnowicki
Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY.
Xiuzhong
X
Zheng
Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY.
Hui
H
Xu
Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
Yeriel D
YD
Estrada
Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY.
Irma
I
Cardinale
Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY; Center for Clinical and Translational Science, The Rockefeller University, New York, NY.
Mayte
M
Suárez-Fariñas
Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY; Center for Clinical and Translational Science, The Rockefeller University, New York, NY.
James G
JG
Krueger
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.
Emma
E
Guttman-Yassky
D000328:Adult; D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D017449:Dermatitis, Allergic Contact / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006241:Haptens / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009532:Nickel / Q000276:immunology / Q000494:pharmacology; D010328:Patch Tests; D010476:Perfume / Q000494:pharmacology; D010577:Petrolatum / Q000494:pharmacology; D012408:Rubber / Q000494:pharmacology; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D058408:Th1-Th2 Balance / Q000187:drug effects; D059467:Transcriptome / Q000276:immunology*
D000485:Allergens; D015703:Antigens, CD; D016207:Cytokines; D006241:Haptens; D010476:Perfume; D009532:Nickel; D010577:Petrolatum; D012408:Rubber
Allergic contact dermatitis; T-cell polarization; allergens; fragrance; human skin; nickel; patch testing; rubber