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.
Tonel
Giulia
G
St. John's Institute of Dermatology, National Institute for Health Research Biomedical Research Centre, King's College London, London, United Kingdom.
Conrad
Curdin
C
Laggner
Ute
U
Di Meglio
Paola
P
Grys
Katarzyna
K
McClanahan
Terrill K
TK
Blumenschein
Wendy M
WM
Qin
Jian-Zhong
JZ
Xin
Hong
H
Oldham
Elizabeth
E
Kastelein
Robert
R
Nickoloff
Brian J
BJ
Nestle
Frank O
FO
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