title: Low expression of the IL-23/Th17 pathway in atopic dermatitis compared to psoriasis.
abstract: The classical Th1/Th2 paradigm previously defining atopic dermatitis (AD) and psoriasis has recently been challenged with the discovery of Th17 T cells that synthesize IL-17 and IL-22. Although it is becoming evident that many Th1 diseases including psoriasis have a strong IL-17 signal, the importance of Th17 T cells in AD is still unclear. We examined and compared skin biopsies from AD and psoriasis patients by gene microarray, RT-PCR, immunohistochemistry, and immunofluorescence. We found a reduced genomic expression of IL-23, IL-17, and IFN-gamma in AD compared with psoriasis. To define the effects of IL-17 and IL-22 on keratinocytes, we performed gene array studies with cytokine-treated keratinocytes. We found lipocalin 2 and numerous other innate defense genes to be selectively induced in keratinocytes by IL-17. IFN-gamma had no effect on antimicrobial gene-expression in keratinocytes. In AD skin lesions, protein and mRNA expression of lipocalin 2 and other innate defense genes (hBD2, elafin, LL37) were reduced compared with psoriasis. Although AD has been framed by the Th1/Th2 paradigm as a Th2 polar disease, we present evidence that the IL-23/Th17 axis is largely absent, perhaps accounting for recurrent skin infections in this disease.
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY 10021, USA.
authors.forename: Emma
authors.initials: E
authors.lastname: Guttman-Yassky
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Lowes
authors.forename: Judilyn
authors.initials: J
authors.lastname: Fuentes-Duculan
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Zaba
authors.forename: Irma
authors.initials: I
authors.lastname: Cardinale
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Nograles
authors.forename: Artemis
authors.initials: A
authors.lastname: Khatcherian
authors.forename: Inna
authors.initials: I
authors.lastname: Novitskaya
authors.forename: John A
authors.initials: JA
authors.lastname: Carucci
authors.forename: Reuven
authors.initials: R
authors.lastname: Bergman
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
mesh_terms: D000209:Acute-Phase Proteins / Q000096:biosynthesis / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology; D053759:Interleukin-23 / Q000096:biosynthesis* / Q000276:immunology; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism; D000071068:Lipocalin-2; D054834:Lipocalins / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000276:immunology; D011565:Psoriasis / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D000209:Acute-Phase Proteins; D007371:Interferon-gamma; D020381:Interleukin-17; D053759:Interleukin-23; D007378:Interleukins; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D000097043:Interleukin-22; C489506:LCN2 protein, human