Interleukin 21 Is a Double-Edged Sword in the SLE-like Disease of BXSB.Yaa Mice

• Published in: The Journal of immunology (1950) 2013-09, Vol.191 (9)
• Main Authors: McPhee, Caroline G., Bubier, Jason A., Sproule, Thomas J., Park, Giljun, Steinbuck, Martin P., Schott, William H., Christianson, Gregory J., Morse, Herbert C., Roopenian, Derry C.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1300439

The pleiotropic cytokine, Interleukin 21 (IL21) is implicated in the pathogenesis of human systemic lupus erythematosus (SLE) by polymorphisms in the molecule and its receptor (IL21R). The SLE-like autoimmune disease of BXSB. Yaa mice is critically dependent on IL21 signaling, providing a model for understanding IL21/IL21R signaling in lupus pathogenesis. Here, we generated BXSB. Yaa mice selectively deficient in IL21R on B cells, on all T cells or on CD8 + T cells alone and examined the effects on disease. We found that IL21 signaling to B cells is essential for the development of all classical disease manifestations, but that IL21 signaling also supports the expansion of central memory, CD8 + suppressor cells and broadly represses the cytokine activity of CD4 + T cells. These results indicate that IL21 has both disease-promoting and disease-suppressive effects in the autoimmune disease of BXSB. Yaa mice.