Document Detail


Cutting edge: A critical functional role for IL-23 in psoriasis.
MedLine Citation:
PMID:  20956338     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Interleukin-23 is a key cytokine involved in the generation of Th17 effector cells. Clinical efficacy of an anti-p40 mAb blocking both IL-12 and IL-23 and disease association with single nucleotide polymorphisms in the IL23R gene raise the question of a functional role of IL-23 in psoriasis. In this study, we provide a comprehensive analysis of IL-23 and its receptor in psoriasis and demonstrate its functional importance in a disease-relevant model system. The expression of IL-23 and its receptor was increased in the tissues of patients with psoriasis. Injection of a mAb specifically neutralizing human IL-23 showed IL-23-dependent inhibition of psoriasis development comparable to the use of anti-TNF blockers in a clinically relevant xenotransplant mouse model of psoriasis. Together, our results identify a critical functional role for IL-23 in psoriasis and provide the rationale for new treatment strategies in chronic epithelial inflammatory disorders.
Authors:
Giulia Tonel; Curdin Conrad; Ute Laggner; Paola Di Meglio; Katarzyna Grys; Terrill K McClanahan; Wendy M Blumenschein; Jian-Zhong Qin; Hong Xin; Elizabeth Oldham; Robert Kastelein; Brian J Nickoloff; Frank O Nestle
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-10-18
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  185     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-04     Completed Date:  2010-12-02     Revised Date:  2011-01-21    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5688-91     Citation Subset:  AIM; IM    
Affiliation:
St. John's Institute of Dermatology, National Institute for Health Research Biomedical Research Centre, King's College London, London, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / therapeutic use
Cell Separation
Disease Models, Animal
Flow Cytometry
Humans
Immunohistochemistry
Interleukin-23 / antagonists & inhibitors*,  immunology*
Mice
Psoriasis / drug therapy,  immunology*,  metabolism
Receptors, Interleukin / immunology,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
ID/Acronym/Agency:
G0601387//Medical Research Council; GR078173MA//Wellcome Trust; R01AR040065/AR/NIAMS NIH HHS; //Department of Health
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/IL23R protein, human; 0/Interleukin-23; 0/Receptors, Interleukin
Comments/Corrections
Comment In:
Nat Rev Rheumatol. 2011 Jan;7(1):4

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