Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain (letter to the editor)

Cua, Daniel J., Sherlock, Jonathan, Chen, Yi, Murphy, Craig A., Joyce, Barbara, Seymour, Brian, Lucian, Linda, To, Wayne, Kwan, Sylvia, Churakova, Tatyana, Zurawski, Sandra, Wiekowski, Maria, Lira, Sergio A., Gorman, Daniel, Kastelein, Robert A. and Sedgwick, Jonathon D. (2003) Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain (letter to the editor). Nature, 421 6924: 744-748. doi:10.1038/nature01355


Author Cua, Daniel J.
Sherlock, Jonathan
Chen, Yi
Murphy, Craig A.
Joyce, Barbara
Seymour, Brian
Lucian, Linda
To, Wayne
Kwan, Sylvia
Churakova, Tatyana
Zurawski, Sandra
Wiekowski, Maria
Lira, Sergio A.
Gorman, Daniel
Kastelein, Robert A.
Sedgwick, Jonathon D.
Title Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain (letter to the editor)
Journal name Nature   Check publisher's open access policy
ISSN 0028-0836
1476-4687
Publication date 2003-02-13
Year available 2003
Sub-type Article (original research)
DOI 10.1038/nature01355
Volume 421
Issue 6924
Start page 744
End page 748
Total pages 5
Place of publication London, UK
Publisher Nature Publishing Group
Language eng
Subject 06 Biological Sciences
Abstract Interleukin-12 (IL-12) is a heterodimeric molecule composed of p35 and p40 subunits. Analyses in vitro have defined IL-12 as an important factor for the differentiation of naive T cells into T-helper type 1 CD4+ lymphocytes secreting interferon-gamma (refs 1, 2). Similarly, numerous studies have concluded that IL-12 is essential for T-cell-dependent immune and inflammatory responses in vivo, primarily through the use of IL-12 p40 gene-targeted mice and neutralizing antibodies against p40. The cytokine IL-23, which comprises the p40 subunit of IL-12 but a different p19 subunit, is produced predominantly by macrophages and dendritic cells, and shows activity on memory T cells. Evidence from studies of IL-23 receptor expression and IL-23 overexpression in transgenic mice suggest, however, that IL-23 may also affect macrophage function directly. Here we show, by using gene-targeted mice lacking only IL-23 and cytokine replacement studies, that the perceived central role for IL-12 in autoimmune inflammation, specifically in the brain, has been misinterpreted and that IL-23, and not IL-12, is the critical factor in this response. In addition, we show that IL-23, unlike IL-12, acts more broadly as an end-stage effector cytokine through direct actions on macrophages.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: School of Chemistry and Molecular Biosciences
School of Medicine Publications
 
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