Cutting edge: A critical functional role for IL-23 in psoriasis.
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.
St. John's Institute of Dermatology, National Institute for Health Research Biomedical Research Centre, King's College London, London, United Kingdom.
Giulia
G
Tonel
Curdin
C
Conrad
Ute
U
Laggner
Paola
P
Di Meglio
Katarzyna
K
Grys
Terrill K
TK
McClanahan
Wendy M
WM
Blumenschein
Jian-Zhong
JZ
Qin
Hong
H
Xin
Elizabeth
E
Oldham
Robert
R
Kastelein
Brian J
BJ
Nickoloff
Frank O
FO
Nestle
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002469:Cell Separation; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D053759:Interleukin-23 / Q000037:antagonists & inhibitors* / Q000276:immunology*; D051379:Mice; D011565:Psoriasis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D018123:Receptors, Interleukin / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000911:Antibodies, Monoclonal; C515500:IL23R protein, human; D053759:Interleukin-23; D018123:Receptors, Interleukin