IL-21 Is a Double-Edged Sword in the Systemic Lupus Erythematosus-like Disease of BXSB.Yaa Mice.
J Immunol 2013 Nov 1; 191(9):4581-8.
The pleiotropic cytokine IL-21 is implicated in the pathogenesis of human systemic lupus erythematosus by polymorphisms in the molecule and its receptor (IL-21R). The systemic lupus erythematosus-like autoimmune disease of BXSB.Yaa mice is critically dependent on IL-21 signaling, providing a model for understanding IL-21/IL-21R signaling in lupus pathogenesis. In this study, we generated BXSB.Yaa mice selectively deficient in IL-21R on B cells, on all T cells, or on CD8(+) T cells alone and examined the effects on disease. We found that IL-21 signaling to B cells is essential for the development of all classical disease manifestations, but that IL-21 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 IL-21 has both disease-promoting and disease-suppressive effects in the autoimmune disease of BXSB.Yaa mice. J Immunol 2013 Nov 1; 191(9):4581-8.
McPhee, Caroline G.; Bubier, Jason A.; Sproule, Thomas J.; Park, Giljun; Steinbuck, Martin P; Schott, William H.; Christianson, Gregory J.; Morse, Herbert C; and Roopenian, Derry C., "IL-21 Is a Double-Edged Sword in the Systemic Lupus Erythematosus-like Disease of BXSB.Yaa Mice." (2013). Faculty Research 2013. 161.