TY - JOUR
T1 - Major differences in inflammatory dendritic cells and their products distinguish atopic dermatitis from psoriasis
AU - Guttman-Yassky, Emma
AU - Lowes, Michelle A.
AU - Fuentes-Duculan, Judilyn
AU - Whynot, Julia
AU - Novitskaya, Inna
AU - Cardinale, Irma
AU - Haider, Asifa
AU - Khatcherian, Artemis
AU - Carucci, John A.
AU - Bergman, Reuven
AU - Krueger, James G.
PY - 2007/5
Y1 - 2007/5
N2 - Background: Atopic dermatitis (AD) and psoriasis represent contrasting poles of the TH1 versus TH2 paradigm. Both diseases have been associated with increased numbers of dendritic cells (DCs) in the skin, but the similarities and differences in DC populations need to be established. Objective: We aimed to characterize the specific DC subsets, as well as chemokine and cytokine environment in chronic AD compared with psoriasis. Methods: Skin biopsies were obtained from patients with acute exacerbation of chronic AD (n = 18), psoriasis (n = 15), and healthy volunteers (n = 15) for microarray analysis, RT-PCR, immunohistochemistry, and double-label immunofluorescence. Results: Myeloid DCs upregulate CCL17 and CCL18 in AD, as opposed to TNF-α and inducible nitric oxide synthase (iNOS) in psoriasis. In our study, we identified cells phenotypically identical to the inflammatory dendritic epidermal cells in the dermis in both diseases, although to a lesser extent in psoriasis. We found substantially higher numbers of dermal CCL22 producing plasmacytoid DCs in AD. The thymic stromal lymphopoietin receptor showed significantly higher expression in AD, whereas the thymic stromal lymphopoietin ligand was upregulated more in psoriasis. Conclusion: There are major differences in myeloid and plasmacytoid subsets of cutaneous DCs and the chemokine/cytokine environment between AD and psoriasis. Distinct subsets within the CD11c+ population may influence polarization through the production of regulatory mediators, including iNOS, TNF, CCL17, and CCL18. Plasmacytoid DCs may also influence TH2 polarization, having a more important role in AD than previously appreciated. Clinical implications: Dermal inflammatory dendritic cells in AD and TNF and iNOS-producing DCs in psoriasis, and/or their regulatory products, may be potential targets for future therapeutic interventions.
AB - Background: Atopic dermatitis (AD) and psoriasis represent contrasting poles of the TH1 versus TH2 paradigm. Both diseases have been associated with increased numbers of dendritic cells (DCs) in the skin, but the similarities and differences in DC populations need to be established. Objective: We aimed to characterize the specific DC subsets, as well as chemokine and cytokine environment in chronic AD compared with psoriasis. Methods: Skin biopsies were obtained from patients with acute exacerbation of chronic AD (n = 18), psoriasis (n = 15), and healthy volunteers (n = 15) for microarray analysis, RT-PCR, immunohistochemistry, and double-label immunofluorescence. Results: Myeloid DCs upregulate CCL17 and CCL18 in AD, as opposed to TNF-α and inducible nitric oxide synthase (iNOS) in psoriasis. In our study, we identified cells phenotypically identical to the inflammatory dendritic epidermal cells in the dermis in both diseases, although to a lesser extent in psoriasis. We found substantially higher numbers of dermal CCL22 producing plasmacytoid DCs in AD. The thymic stromal lymphopoietin receptor showed significantly higher expression in AD, whereas the thymic stromal lymphopoietin ligand was upregulated more in psoriasis. Conclusion: There are major differences in myeloid and plasmacytoid subsets of cutaneous DCs and the chemokine/cytokine environment between AD and psoriasis. Distinct subsets within the CD11c+ population may influence polarization through the production of regulatory mediators, including iNOS, TNF, CCL17, and CCL18. Plasmacytoid DCs may also influence TH2 polarization, having a more important role in AD than previously appreciated. Clinical implications: Dermal inflammatory dendritic cells in AD and TNF and iNOS-producing DCs in psoriasis, and/or their regulatory products, may be potential targets for future therapeutic interventions.
KW - Atopic dermatitis
KW - TIP-DCs
KW - inflammatory dendritic epidermal cells
KW - myeloid DCs
KW - plasmacytoid DCs
KW - psoriasis
UR - http://www.scopus.com/inward/record.url?scp=34247532495&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34247532495&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2007.03.006
DO - 10.1016/j.jaci.2007.03.006
M3 - Article
C2 - 17472813
AN - SCOPUS:34247532495
SN - 0091-6749
VL - 119
SP - 1210
EP - 1217
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 5
ER -