Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain

Daniel J. Cua (), Jonathan Sherlock, Yi Chen, Craig A. Murphy, Barbara Joyce, Brian Seymour, Linda Lucian, Wayne To, Sylvia Kwan, Tatyana Churakova, Sandra Zurawski, Maria Wiekowski, Sergio A. Lira, Daniel Gorman, Robert A. Kastelein and Jonathon D. Sedgwick
Additional contact information
Daniel J. Cua: DNAX Research Inc.
Jonathan Sherlock: DNAX Research Inc.
Yi Chen: DNAX Research Inc.
Craig A. Murphy: DNAX Research Inc.
Barbara Joyce: DNAX Research Inc.
Brian Seymour: DNAX Research Inc.
Linda Lucian: DNAX Research Inc.
Wayne To: DNAX Research Inc.
Sylvia Kwan: DNAX Research Inc.
Tatyana Churakova: DNAX Research Inc.
Sandra Zurawski: DNAX Research Inc.
Maria Wiekowski: Schering-Plough Research Institute
Sergio A. Lira: Schering-Plough Research Institute
Daniel Gorman: DNAX Research Inc.
Robert A. Kastelein: DNAX Research Inc.
Jonathon D. Sedgwick: DNAX Research Inc.

Nature, 2003, vol. 421, issue 6924, 744-748

Abstract: 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-γ (refs 1, 2). Similarly, numerous studies3,4,5,6,7 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 subunit8, is produced predominantly by macrophages and dendritic cells, and shows activity on memory T cells. Evidence from studies of IL-23 receptor expression9 and IL-23 overexpression in transgenic mice10 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.

Date: 2003
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/nature01355 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:421:y:2003:i:6924:d:10.1038_nature01355

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature01355

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().