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

@article{cua_interleukin-23_2003, 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.}, author = {Cua, Daniel J. and Sherlock, Jonathan and Chen, Yi and Murphy, Craig A. and Joyce, Barbara and Seymour, Brian and Lucian, Linda and To, Wayne and Kwan, Sylvia and Churakova, Tatyana and Zurawski, Sandra and Wiekowski, Maria and Lira, Sergio A. and Gorman, Daniel and Kastelein, Robert A. and Sedgwick, Jonathon D.}, citeulike-article-id = {2705455}, comment = {PMID: 12610626}, journal = {Nature}, keywords = {autoimmunity, il-12, il-23}, month = {February}, pages = {744--8}, posted-at = {2008-04-23 05:48:15}, priority = {0}, title = {Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain}, volume = {421}, year = {2003} }

TY - JOUR ID - cua_interleukin-23_2003 L3 - citeulike-article-id:2705455 N2 - 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. JF - Nature EP - 8 TI - Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain VL - 421 SP - 744 KW - autoimmunity KW - il-12 KW - il-23 N1 - PMID: 12610626 AU - Cua, Daniel AU - Sherlock, Jonathan AU - Chen, Yi AU - Murphy, Craig AU - Joyce, Barbara AU - Seymour, Brian AU - Lucian, Linda AU - To, Wayne AU - Kwan, Sylvia AU - Churakova, Tatyana AU - Zurawski, Sandra AU - Wiekowski, Maria AU - Lira, Sergio AU - Gorman, Daniel AU - Kastelein, Robert AU - Sedgwick, Jonathon PY - 2003/February// ER -