A critical role for IL-21 receptor signaling in the pathogenesis of systemic lupus erythematosus in BXSB-Yaa mice.
Document Type
Article
Publication Date
2009
Keywords
Antibody-Formation, Base-Sequence, DNA-Primers, Enzyme-Linked-Immunosorbent-Assay, Flow-Cytometry, Interleukins, Kidney-Diseases, Lupus-Erythematosus-Systemic, Lymphocyte-Subsets, Mice, Receptors-Interleukin-21
First Page
1518
Last Page
1523
JAX Source
Proc Natl Acad Sci U S A 2009 Feb; 106(5):1518-23.
Abstract
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.
Recommended Citation
Bubier JA,
Sproule TJ,
Foreman O,
Spolski R,
Shaffer DJ,
Morse HC,
Leonard WJ,
Roopenian DC.
A critical role for IL-21 receptor signaling in the pathogenesis of systemic lupus erythematosus in BXSB-Yaa mice. Proc Natl Acad Sci U S A 2009 Feb; 106(5):1518-23.