Unknown

Dataset Information

0

A critical role for IL-21 receptor signaling in the pathogenesis of systemic lupus erythematosus in BXSB-Yaa mice.


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.

SUBMITTER: Bubier JA 

PROVIDER: S-EPMC2635818 | biostudies-other | 2009 Feb

REPOSITORIES: biostudies-other

altmetric image

Publications

A critical role for IL-21 receptor signaling in the pathogenesis of systemic lupus erythematosus in BXSB-Yaa mice.

Bubier Jason A JA   Sproule Thomas J TJ   Foreman Oded O   Spolski Rosanne R   Shaffer Daniel J DJ   Morse Herbert C HC   Leonard Warren J WJ   Roopenian Derry C DC  

Proceedings of the National Academy of Sciences of the United States of America 20090121 5


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 BX  ...[more]

Similar Datasets

| S-EPMC7686966 | biostudies-literature
| S-EPMC3807747 | biostudies-literature
| S-EPMC2669395 | biostudies-literature
| S-EPMC4079820 | biostudies-literature
| S-EPMC4654374 | biostudies-other
| S-EPMC3704198 | biostudies-literature
| S-EPMC6362534 | biostudies-literature
| S-EPMC7157613 | biostudies-literature
| S-EPMC6940927 | biostudies-literature
| S-EPMC4244532 | biostudies-literature