Treatment of BXSB-Yaa mice with IL-21R-Fc fusion protein minimally attenuates systemic lupus erythematosus.
Interleukin-21 (IL-21) is a pleiotropic cytokine whose function is only now being unraveled. Abundant evidence indicates that activated CD4 T cells are the primary, if not the only, source of IL-21. While it is clear that IL-21 is actively transcribed by naïve activated T cells, recent studies have shown that IL-21 potentially promotes a developmental shift of naïve T cells toward the Th2 phenotype. BXSB-Yaa mice develop an autoimmune syndrome similar to systemic lupus erythematosus (SLE), affecting males earlier than females on account of the presence of the Yaa (Y-linked autoimmune acceleration) locus. Previous results indicate the elevation of IL-21 expression by BXSB-Yaa mice at an age when the early characteristics of autoimmune processes first become evident. We set out to determine whether IL-21 was necessary for disease progression in BXSB-Yaa mice. Mice were treated for 24 weeks with soluble IL-21R-Fc in order to therapeutically neutralize the IL-21 present. The results overall suggest a biphasic effect of IL-21, negatively influencing survival early on and positively influencing survival at later stages. We propose that IL-21 exerts a pleiotropic effect in which it promotes the protective effects of CD8+ suppressor cells in the early disease phase and then promotes the humoral components of SLE in the later disease stages. This experiment provides preliminary evidence for a role of IL-21 in modulating the severity of SLE in BXSB-Yaa mice.
Bubier
J A
JA
The Jackson Laboratory, 600 Main St. Bar Harbor, ME 04609, USA.
Bennett
S M
SM
Sproule
T J
TJ
Lyons
B L
BL
Olland
S
S
Young
D A
DA
Roopenian
D C
DC
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015432:Glomerulonephritis, Membranoproliferative / Q000276:immunology / Q000473:pathology; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D007167:Immunotherapy; D053738:Interleukin-21 Receptor alpha Subunit / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use*; D007378:Interleukins / Q000378:metabolism; D007668:Kidney / Q000502:physiology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D013154:Spleen / Q000378:metabolism; D015996:Survival Rate; D014158:Transcription, Genetic / Q000235:genetics; D000098546:Interleukin-21
C508118:Il21r protein, mouse; D007141:Immunoglobulin Fc Fragments; D053738:Interleukin-21 Receptor alpha Subunit; D007378:Interleukins; D000098546:Interleukin-21