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.
['Dhingra|Nikhil|N|', 'Shemer|Avner|A|', 'Correa da Rosa|Joel|J|', 'Rozenblit|Mariya|M|', 'Fuentes-Duculan|Judilyn|J|', 'Gittler|Julia K|JK|', 'Finney|Robert|R|', 'Czarnowicki|Tali|T|', 'Zheng|Xiuzhong|X|', 'Xu|Hui|H|', 'Estrada|Yeriel D|YD|', 'Cardinale|Irma|I|', 'Suárez-Fariñas|Mayte|M|', 'Krueger|James G|JG|', 'Guttman-Yassky|Emma|E|']
D000328:Adult D000485:Allergens D000818:Animals D015703:Antigens, CD D016207:Cytokines D017449:Dermatitis, Allergic Contact D005260:Female D020869:Gene Expression Profiling D006241:Haptens D006801:Humans D008297:Male D051379:Mice D008875:Middle Aged D009532:Nickel D010328:Patch Tests D010476:Perfume D010577:Petrolatum D012408:Rubber D012867:Skin D013045:Species Specificity D016176:T-Lymphocyte Subsets D058408:Th1-Th2 Balance D059467:Transcriptome
Allergic contact dermatitis nickel T-cell polarization allergens fragrance rubber human skin patch testing