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...
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| Veröffentlicht in: | The Journal of immunology (1950) 2010-11, Vol.185 (10), p.5688-5691 |
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| container_title | The Journal of immunology (1950) |
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| creator | Tonel, Giulia Conrad, Curdin Laggner, Ute Di Meglio, Paola Grys, Katarzyna McClanahan, Terrill K Blumenschein, Wendy M Qin, Jian-Zhong Xin, Hong Oldham, Elizabeth Kastelein, Robert Nickoloff, Brian J Nestle, Frank O |
| description | 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. |
| doi_str_mv | 10.4049/jimmunol.1001538 |
| format | Article |
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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.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.1001538</identifier><identifier>PMID: 20956338</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Antibodies, Monoclonal - therapeutic use ; Cell Separation ; Disease Models, Animal ; Flow Cytometry ; Humans ; Immunohistochemistry ; Interleukin-23 - antagonists & inhibitors ; Interleukin-23 - immunology ; Mice ; Psoriasis - drug therapy ; Psoriasis - immunology ; Psoriasis - metabolism ; Receptors, Interleukin - immunology ; Receptors, Interleukin - metabolism ; Reverse Transcriptase Polymerase Chain Reaction</subject><ispartof>The Journal of immunology (1950), 2010-11, Vol.185 (10), p.5688-5691</ispartof><rights>Copyright © 2010 by The American Association of Immunologists, Inc. All rights reserved. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c493t-9e28e2f1bf87e560fb4010902735967deea2010579938220a9f142bbdb8c30cb3</citedby><cites>FETCH-LOGICAL-c493t-9e28e2f1bf87e560fb4010902735967deea2010579938220a9f142bbdb8c30cb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20956338$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tonel, Giulia</creatorcontrib><creatorcontrib>Conrad, Curdin</creatorcontrib><creatorcontrib>Laggner, Ute</creatorcontrib><creatorcontrib>Di Meglio, Paola</creatorcontrib><creatorcontrib>Grys, Katarzyna</creatorcontrib><creatorcontrib>McClanahan, Terrill K</creatorcontrib><creatorcontrib>Blumenschein, Wendy M</creatorcontrib><creatorcontrib>Qin, Jian-Zhong</creatorcontrib><creatorcontrib>Xin, Hong</creatorcontrib><creatorcontrib>Oldham, Elizabeth</creatorcontrib><creatorcontrib>Kastelein, Robert</creatorcontrib><creatorcontrib>Nickoloff, Brian J</creatorcontrib><creatorcontrib>Nestle, Frank O</creatorcontrib><title>Cutting edge: A critical functional role for IL-23 in psoriasis</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>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.</description><subject>Animals</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Cell Separation</subject><subject>Disease Models, Animal</subject><subject>Flow Cytometry</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Interleukin-23 - antagonists & inhibitors</subject><subject>Interleukin-23 - immunology</subject><subject>Mice</subject><subject>Psoriasis - drug therapy</subject><subject>Psoriasis - immunology</subject><subject>Psoriasis - metabolism</subject><subject>Receptors, Interleukin - immunology</subject><subject>Receptors, Interleukin - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkbtPwzAQxi0EgvLYmVA2ppSzHb8YQFXFo1IlFpgtx3WKqyQudoLEf0-qlgompjvdfffpO_0QusQwLqBQNyvfNH0b6jEGwIzKAzTCjEHOOfBDNAIgJMeCixN0mtIKADiQ4hidEFCMUypH6H7ad51vl5lbLN1tNsls9J23ps6qvrWdD-3QxlC7rAoxm81zQjPfZusUojfJp3N0VJk6uYtdPUNvjw-v0-d8_vI0m07muS0U7XLliHSkwmUlhWMcqrIADAqIoExxsXDOkGHAhFJUEgJGVbggZbkopaVgS3qG7ra-675s3MK6toum1uvoGxO_dDBe_920_l0vw6emQnAq8WBwvTOI4aN3qdONT9bVtWld6JOWjAsmCSf_KgUnhdykHZSwVdoYUoqu2ufBoDeA9A8gvQM0nFz9_mN_8EOEfgN2UY0F</recordid><startdate>20101115</startdate><enddate>20101115</enddate><creator>Tonel, Giulia</creator><creator>Conrad, Curdin</creator><creator>Laggner, Ute</creator><creator>Di Meglio, Paola</creator><creator>Grys, Katarzyna</creator><creator>McClanahan, Terrill K</creator><creator>Blumenschein, Wendy M</creator><creator>Qin, Jian-Zhong</creator><creator>Xin, Hong</creator><creator>Oldham, Elizabeth</creator><creator>Kastelein, Robert</creator><creator>Nickoloff, Brian J</creator><creator>Nestle, Frank O</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7T5</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20101115</creationdate><title>Cutting edge: A critical functional role for IL-23 in psoriasis</title><author>Tonel, Giulia ; 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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. 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| ispartof | The Journal of immunology (1950), 2010-11, Vol.185 (10), p.5688-5691 |
| issn | 0022-1767 1550-6606 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Animals Antibodies, Monoclonal - therapeutic use Cell Separation Disease Models, Animal Flow Cytometry Humans Immunohistochemistry Interleukin-23 - antagonists & inhibitors Interleukin-23 - immunology Mice Psoriasis - drug therapy Psoriasis - immunology Psoriasis - metabolism Receptors, Interleukin - immunology Receptors, Interleukin - metabolism Reverse Transcriptase Polymerase Chain Reaction |
| title | Cutting edge: A critical functional role for IL-23 in psoriasis |
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