Divergent Pro- and Antiinflammatory Roles for IL-23 and IL-12 in Joint Autoimmune Inflammation
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- Craig A. Murphy
- 1Discovery Research, DNAX Research Inc., Palo Alto, CA 94304
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- Claire L. Langrish
- 1Discovery Research, DNAX Research Inc., Palo Alto, CA 94304
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- Yi Chen
- 1Discovery Research, DNAX Research Inc., Palo Alto, CA 94304
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- Wendy Blumenschein
- 2Experimental Pathology and Pharmacology, DNAX Research Inc., Palo Alto, CA 94304
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- Terrill McClanahan
- 2Experimental Pathology and Pharmacology, DNAX Research Inc., Palo Alto, CA 94304
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- Robert A. Kastelein
- 1Discovery Research, DNAX Research Inc., Palo Alto, CA 94304
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- Jonathon D. Sedgwick
- 1Discovery Research, DNAX Research Inc., Palo Alto, CA 94304
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- Daniel J. Cua
- 1Discovery Research, DNAX Research Inc., Palo Alto, CA 94304
説明
<jats:p>Interleukin (IL) 23 is a heterodimeric cytokine composed of a p19 subunit and the p40 subunit of IL-12. IL-23 affects memory T cell and inflammatory macrophage function through engagement of a novel receptor (IL-23R) on these cells. Recent analysis of the contribution of IL-12 and IL-23 to central nervous system autoimmune inflammation demonstrated that IL-23 rather than IL-12 was the essential cytokine. Using gene-targeted mice lacking only IL-12 (p35−/−) or IL-23 (p19−/−), we show that the specific absence of IL-23 is protective, whereas loss of IL-12 exacerbates collagen-induced arthritis. IL-23 gene-targeted mice did not develop clinical signs of disease and were completely resistant to the development of joint and bone pathology. Resistance correlated with an absence of IL-17–producing CD4+ T cells despite normal induction of collagen-specific, interferon-γ–producing T helper 1 cells. In contrast, IL-12–deficient p35−/− mice developed more IL-17–producing CD4+ T cells, as well as elevated mRNA expression of proinflammatory tumor necrosis factor, IL-1β, IL-6, and IL-17 in affected tissues of diseased mice. The data presented here indicate that IL-23 is an essential promoter of end-stage joint autoimmune inflammation, whereas IL-12 paradoxically mediates protection from autoimmune inflammation.</jats:p>
収録刊行物
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- The Journal of Experimental Medicine
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The Journal of Experimental Medicine 198 (12), 1951-1957, 2003-12-08
Rockefeller University Press
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詳細情報 詳細情報について
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- CRID
- 1361981471112943232
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- NII論文ID
- 30017417371
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- ISSN
- 15409538
- 00221007
- http://id.crossref.org/issn/00221007
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- データソース種別
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- Crossref
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