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Treatment of BXSB‐ Yaa Mice with IL‐21R‐Fc Fusion Protein Minimally Attenuates Systemic Lupus Erythematosus
Author(s) -
BUBIER J.A.,
BENNETT S.M.,
SPROULE T.J.,
LYONS B.L.,
OLLAND S.,
YOUNG D.A.,
ROOPENIAN D.C.
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1423.063
Subject(s) - immunology , autoimmunity , autoimmune disease , cd8 , cytokine , disease , phenotype , immune system , medicine , systemic lupus erythematosus , interleukin , lupus erythematosus , biology , antibody , gene , genetics
: 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.