Cutting edge: IL-23 receptor deficiency prevents the development of lupus nephritis in C57BL/6-lpr/lpr mice

• Published in: The Journal of immunology (1950) Vol. 184; no. 9; pp. 4605 - 4609
• Main Authors: Kyttaris, Vasileios C, Zhang, Zheng, Kuchroo, Vijay K, Oukka, Mohamed, Tsokos, George C
• Format: Journal Article
• Language: English
• Published: United States 01.05.2010
• Subjects: Animals; Autoantibodies - biosynthesis; Autoantibodies - metabolism; Cell Movement - genetics; Cell Movement - immunology; Cells, Cultured; Crosses, Genetic; Cytokines - antagonists & inhibitors; Cytokines - biosynthesis; Genetic Predisposition to Disease; Hyperplasia - genetics; Hyperplasia - immunology; Hyperplasia - prevention & control; Inflammation Mediators - antagonists & inhibitors; Inflammation Mediators - metabolism; Interleukin-17 - biosynthesis; Lupus Nephritis - genetics; Lupus Nephritis - immunology; Lupus Nephritis - pathology; Lupus Nephritis - prevention & control; Lymphoid Tissue - cytology; Lymphoid Tissue - immunology; Lymphoid Tissue - pathology; Mice; Mice, Inbred C57BL; Mice, Inbred MRL lpr; Mice, Knockout; Receptors, Interleukin - deficiency; Receptors, Interleukin - genetics
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0903595

IL-17-producing T cells infiltrate kidneys of patients with lupus nephritis, and IL-23-treated lymph node cells from lupus-prone mice may transfer disease to Rag1-deficient mice. In this study, we show that IL-23R-deficient lupus-prone C57BL/6-lpr/lpr mice display decreased numbers of CD3(+)CD4(-)CD8(-) cells and IL-17A-producing cells in the lymph nodes and produce less anti-DNA Abs. In addition, clinical and pathology measures of lupus nephritis are abrogated. The presented experiments document the importance of IL-23R-mediated signaling in the development of lupus nephritis and urge the consideration of proper biologics for the treatment of the disease.