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41.
Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain 总被引:118,自引:0,他引:118
Cua DJ Sherlock J Chen Y Murphy CA Joyce B Seymour B Lucian L To W Kwan S Churakova T Zurawski S Wiekowski M Lira SA Gorman D Kastelein RA Sedgwick JD 《Nature》2003,421(6924):744-748
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. 相似文献
42.
A. Samali A. M. Gorman T. G. Cotter 《Cellular and molecular life sciences : CMLS》1996,52(10-11):933-941
The process of programmed cell death, or apoptosis, has become one of the most intensively studied topics in biological sciences in the last two decades. Apoptosis as a common and universal mechanism of cell death, distinguishable from necrosis, is now a widely accepted concept after the landmark paper by Kerr, Wyllie and Currie in the early seventies [1]. Different components of the death machinery in eukaryotes are discussed in this issue. 相似文献