A critical role for IL-21 receptor signaling in the pathogenesis of systemic lupus erythematosus in BXSB-Yaa mice.
Antibody-Formation, Base-Sequence, DNA-Primers, Enzyme-Linked-Immunosorbent-Assay, Flow-Cytometry, Interleukins, Kidney-Diseases, Lupus-Erythematosus-Systemic, Lymphocyte-Subsets, Mice, Receptors-Interleukin-21
Proc Natl Acad Sci U S A 2009 Feb; 106(5):1518-23.
Interleukin 21 (IL-21) is a pleiotropic cytokine produced by CD4 T cells that affects the differentiation and function of T, B, and NK cells by binding to a receptor consisting of the common cytokine receptor gamma chain and the IL-21 receptor (IL-21R). IL-21, a product associated with IL-17-producing CD4 T cells (T(H)17) and follicular CD4 T helper cells (T(FH)), has been implicated in autoimmune disorders including the severe systemic lupus erythematosus (SLE)-like disease characteristic of BXSB-Yaa mice. To determine whether IL-21 plays a significant role in this disease, we compared IL-21R-deficient and -competent BXSB-Yaa mice for multiple parameters of SLE. The deficient mice showed none of the abnormalities characteristic of SLE in IL-21R-competent Yaa mice, including hypergammaglobulinemia, autoantibody production, reduced frequencies of marginal zone B cells and monocytosis, renal disease, and premature morbidity. IL-21 production associated with this autoimmune disease was not a product of T(H)17 cells and was not limited to conventional CXCR5(+) T(FH) but instead was produced broadly by ICOS(+) CD4(+) splenic T cells. IL-21 arising from an abnormal population of CD4 T cells is thus central to the development of this lethal disease, and, more generally, could play an important role in human SLE and related autoimmune disorders.
Bubier, J A.; Sproule, T J.; Foreman, O; Spolski, R; Shaffer, D J.; Morse, H C.; Leonard, W J.; and Roopenian, D C., "A critical role for IL-21 receptor signaling in the pathogenesis of systemic lupus erythematosus in BXSB-Yaa mice." (2009). Faculty Research 2000 - 2009. 1910.