Cutting Edge: A Critical Functional Role for IL-23 in Psoriasis

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

doi:10.4049/jimmunol.1001538

Cutting Edge: A Critical Functional Role for IL-23 in Psoriasis

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

Dermatology

Research output: Contribution to journal › Article › peer-review

195 Citations (Scopus)

Abstract

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. The Journal of Immunology, 2010, 185: 5688-5691.

Original language	English
Pages (from-to)	5688 - 5691
Number of pages	4
Journal	Journal of Immunology
Volume	185
Issue number	10
DOIs	https://doi.org/10.4049/jimmunol.1001538
Publication status	Published - 15 Nov 2010

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title = "Cutting Edge: A Critical Functional Role for IL-23 in Psoriasis",

abstract = "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. The Journal of Immunology, 2010, 185: 5688-5691.",

author = "Giulia Tonel and Curdin Conrad and Ute Laggner and {Di Meglio}, Paola and Katarzyna Grys and McClanahan, {Terrill K.} and Blumenschein, {Wendy M.} and Jian-Zhong Qin and Hong Xin and Elizabeth Oldham and Robert Kastelein and Nickoloff, {Brian J.} and Nestle, {Frank O.}",

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doi = "10.4049/jimmunol.1001538",

language = "English",

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T1 - Cutting Edge: A Critical Functional Role for IL-23 in Psoriasis

AU - Tonel, Giulia

AU - Conrad, Curdin

AU - Laggner, Ute

AU - Di Meglio, Paola

AU - Grys, Katarzyna

AU - McClanahan, Terrill K.

AU - Blumenschein, Wendy M.

AU - Qin, Jian-Zhong

AU - Xin, Hong

AU - Oldham, Elizabeth

AU - Kastelein, Robert

AU - Nickoloff, Brian J.

AU - Nestle, Frank O.

PY - 2010/11/15

Y1 - 2010/11/15

N2 - 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. The Journal of Immunology, 2010, 185: 5688-5691.

AB - 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. The Journal of Immunology, 2010, 185: 5688-5691.

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DO - 10.4049/jimmunol.1001538

M3 - Article

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VL - 185

SP - 5688

EP - 5691

JO - Journal of Immunology

JF - Journal of Immunology

IS - 10

ER -

Cutting Edge: A Critical Functional Role for IL-23 in Psoriasis

Abstract

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