Document Detail


Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis.
MedLine Citation:
PMID:  19380832     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Topical application of imiquimod (IMQ), a TLR7/8 ligand and potent immune activator, can induce and exacerbate psoriasis, a chronic inflammatory skin disorder. Recently, a crucial role was proposed for the IL-23/IL-17 axis in psoriasis. We hypothesized that IMQ-induced dermatitis in mice can serve as a model for the analysis of pathogenic mechanisms in psoriasis-like dermatitis and assessed its IL-23/IL-17 axis dependency. Daily application of IMQ on mouse back skin induced inflamed scaly skin lesions resembling plaque type psoriasis. These lesions showed increased epidermal proliferation, abnormal differentiation, epidermal accumulation of neutrophils in microabcesses, neoangiogenesis, and infiltrates consisting of CD4(+) T cells, CD11c(+) dendritic cells, and plasmacytoid dendritic cells. IMQ induced epidermal expression of IL-23, IL-17A, and IL-17F, as well as an increase in splenic Th17 cells. IMQ-induced dermatitis was partially dependent on the presence of T cells, whereas disease development was almost completely blocked in mice deficient for IL-23 or the IL-17 receptor, demonstrating a pivotal role of the IL-23/IL-17 axis. In conclusion, the sole application of the innate TLR7/8 ligand IMQ rapidly induces a dermatitis closely resembling human psoriasis, critically dependent on the IL-23/IL-17 axis. This rapid and convenient model allows further elucidation of pathogenic mechanisms and evaluation of new therapies in psoriasis.
Authors:
Leslie van der Fits; Sabine Mourits; Jane S A Voerman; Marius Kant; Louis Boon; Jon D Laman; Ferry Cornelissen; Anne-Marie Mus; Edwin Florencia; Errol P Prens; Erik Lubberts
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  182     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-04-21     Completed Date:  2009-06-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5836-45     Citation Subset:  AIM; IM    
Affiliation:
Department of Dermatology, Erasmus Medical Center, Rotterdam, The Netherlands. L.vanderfits@lumc.nl
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MeSH Terms
Descriptor/Qualifier:
Aminoquinolines / toxicity*
Animals
Cell Differentiation / drug effects,  immunology
Cell Proliferation / drug effects
Dermatitis, Contact / immunology*,  pathology*
Disease Models, Animal
Humans
Inflammation Mediators / physiology*
Interleukin-17 / metabolism,  physiology*
Interleukin-23 / deficiency,  genetics,  physiology*
Keratinocytes / drug effects,  immunology,  pathology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Psoriasis / chemically induced,  immunology*,  pathology*
Receptors, Interleukin-17 / deficiency,  genetics
Chemical
Reg. No./Substance:
0/Aminoquinolines; 0/Inflammation Mediators; 0/Interleukin-17; 0/Interleukin-23; 0/Receptors, Interleukin-17; 99011-02-6/imiquimod

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


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