Document Detail


Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways.
MedLine Citation:
PMID:  18684158     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
K E Nograles; L C Zaba; E Guttman-Yassky; J Fuentes-Duculan; M Suárez-Fariñas; I Cardinale; A Khatcherian; J Gonzalez; K C Pierson; T R White; C Pensabene; I Coats; I Novitskaya; M A Lowes; J G Krueger
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-08-05
Journal Detail:
Title:  The British journal of dermatology     Volume:  159     ISSN:  1365-2133     ISO Abbreviation:  Br. J. Dermatol.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-11-27     Completed Date:  2009-04-06     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  0004041     Medline TA:  Br J Dermatol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1092-102     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Chronic Disease
Cytokines / genetics,  metabolism*
Flow Cytometry
Fluorescent Antibody Technique / methods
Humans
Immunohistochemistry
Interferon-gamma / metabolism,  pharmacology
Interleukin-17 / metabolism,  pharmacology
Interleukins / metabolism,  pharmacology
Keratinocytes / immunology*,  ultrastructure
Psoriasis / genetics,  immunology*,  pathology
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocytes / drug effects,  immunology*
Tissue Array Analysis
Grant Support
ID/Acronym/Agency:
1 K23 AR052404-01A1/AR/NIAMS NIH HHS; 5UL1RR024143-02/RR/NCRR NIH HHS; GM07739/GM/NIGMS NIH HHS; UL1 RR024143/RR/NCRR NIH HHS; UL1 RR024143-02/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Cytokines; 0/Interleukin-17; 0/Interleukins; 0/interleukin-22; 82115-62-6/Interferon-gamma
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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