IL-21 is a double-edged sword in the systemic lupus erythematosus-like disease of BXSB.Yaa mice.
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.
The Jackson Laboratory, Bar Harbor, ME 04609.
Caroline G
CG
McPhee
Jason A
JA
Bubier
Thomas J
TJ
Sproule
Giljun
G
Park
Martin P
MP
Steinbuck
William H
WH
Schott
Gregory J
GJ
Christianson
Herbert C
HC
Morse
Derry C
DC
Roopenian
D000818:Animals; D001402:B-Lymphocytes; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D053655:Receptors, Interleukin-21 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D000098546:Interleukin-21
D016207:Cytokines; D007378:Interleukins; D053655:Receptors, Interleukin-21; D000098546:Interleukin-21