TY - JOUR
T1 - Molecular profiling of contact dermatitis skin identifies allergen-dependent differences in immune response
AU - Dhingra, Nikhil
AU - Shemer, Avner
AU - Correa Da Rosa, Joel
AU - Rozenblit, Mariya
AU - Fuentes-Duculan, Judilyn
AU - Gittler, Julia K.
AU - Finney, Robert
AU - Czarnowicki, Tali
AU - Zheng, Xiuzhong
AU - Xu, Hui
AU - Estrada, Yeriel D.
AU - Cardinale, Irma
AU - Suárez-Fariñas, Mayte
AU - Krueger, James G.
AU - Guttman-Yassky, Emma
N1 - Funding Information:
J.G.K., M.S.-F., J.C.d.R., M.R., T.C., and N.D. were supported by the National Center for Research Resources (NCRR) (grant no. 5UL1RR024143-02 ), a component of the National Institutes of Health (NIH), and the NIH Roadmap for Medical Research. E.G.-Y. was supported by the Dermatology Foundation Physician Scientist Career Development Award .
PY - 2014/8
Y1 - 2014/8
N2 - 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.
AB - 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.
KW - Allergic contact dermatitis
KW - T-cell polarization
KW - allergens
KW - fragrance
KW - human skin
KW - nickel
KW - patch testing
KW - rubber
UR - http://www.scopus.com/inward/record.url?scp=84905574430&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2014.03.009
DO - 10.1016/j.jaci.2014.03.009
M3 - Article
C2 - 24768652
AN - SCOPUS:84905574430
SN - 0091-6749
VL - 134
SP - 362
EP - 372
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 2
ER -