GeneSet Information

Tier III GS75756 • Keratinocyte genes modulated by IL-17 treatment

DESCRIPTION:

There are discrete populations of IL-17 and IFN-γ-producing T-helper cells in psoriatic and normal dermis and peripheral blood.18 As murine Th17 cells can produce both IL-17 and IL-22,15 we wanted to investigate whether IL-17-producing cells in normal human skin and peripheral blood could also produce IL-22. We assessed expression and localization of receptors for IL-17 (IL-17R) and IL-22 (IL-22R1) on cells in normal human skin using immunohistochemical staining (n = 5).

LABEL:

Kerat. Genes mod. IL-17

SCORE TYPE:

Effect

DATE ADDED:

2010-07-06

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Nograles KE, Zaba LC, Guttman-Yassky E, Fuentes-Duculan J, Surez-Farias M, Cardinale I, Khatcherian A, Gonzalez J, Pierson KC, White TR, Pensabene C, Coats I, Novitskaya I, Lowes MA, Krueger JG

TITLE:

Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways.

JOURNAL:

The British journal of dermatology Nov 2008, Vol 159, pp. 1092-102

ABSTRACT:

BACKGROUND: Psoriasis vulgaris is an inflammatory skin disease mediated by Th1 and Th17 cytokines, yet the relative contribution of interferon (IFN)-gamma, interleukin (IL)-17 and IL-22 on disease pathogenesis is still unknown. OBJECTIVES: In this study, we sought to identify the cytokines produced by skin-resident T cells in normal skin, localize the receptors for these cytokines, and examine how these cytokines alter gene expression profiles of the cells bearing cognate receptors. METHODS: We used intracellular cytokine staining and flow cytometry to evaluate T cell cytokine production, and immunohistochemistry and double-label immunofluorescence to localize cytokine receptors in skin. Gene array analysis of cytokine-treated keratinocytes was performed using moderated paired t-test controlling for false discovery rate using the Benjamini-Hochberg procedure. RESULTS: We demonstrate that T-helper cells producing IL-17, IL-22 and/or IFN-gamma, as well as the cells bearing cognate cytokine receptors, are present in normal human skin. Keratinocytes stimulated with IL-17 expressed chemokines that were different from those induced by IFN-gamma, probably contributing to the influx of neutrophils, dendritic cells and memory T cells into the psoriatic lesion. In contrast, IL-22 downregulated genes associated with keratinocyte differentiation and caused epidermal alterations in an organotypic skin model. CONCLUSIONS: Our results suggest that the Th17 cytokines IL-17 and IL-22 mediate distinct downstream pathways that contribute to the psoriatic phenotype: IL-17 is more proinflammatory, while IL-22 retards keratinocyte differentiation. PUBMED: 18684158
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Annotation Information

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T-Lymphocytes (D013601)
Keratinocytes (D015603)
Memory (D008568)
Humans (D006801)
Receptors, Cytokine (D018121)
Cytokines (D016207)
Psoriasis (D011565)
Dendritic Cells (D003713)
Gene Expression Profiling (D020869)
Skin (D012867)
Immunohistochemistry (D007150)
Th17 Cells (D058504)
Therapeutics (D013812)
Reverse Transcriptase Polymerase Chain Reaction (D020133)
Flow Cytometry (D005434)
Tissue Array Analysis (D046888)
Staining and Labeling (D013194)
Neutrophils (D009504)
Interferon-gamma (D007371)
Interferons (D007372)
Interleukins (D007378)
Cells (D002477)
Chronic Disease (D002908)
Blood (D001769)
Skin Diseases (D012871)
Methods (D008722)
Fluorescent Antibody Technique (D005455)
Chemokines (D018925)
Interleukin-17 (D020381)
Dermis (D020405)
blood (MA:0000059)
skin (MA:0000151)
dermis (MA:0000152)
psoriasis (MP:0001193)
cell (GO:0005623)
intracellular (GO:0005622)
keratinocyte differentiation (GO:0030216)
pathogenesis (GO:0009405)
T cell cytokine production (GO:0002369)
localization (GO:0051179)
cytokine production (GO:0001816)
gene expression (GO:0010467)
memory (GO:0007613)

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Supported by NIH R01 AA18776 jointly funded by NIAAA and NIDA, and JAX Center for Precision Genetics NIH U54 OD 020351