کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5666734 | 1591541 | 2017 | 11 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: PKK deficiency in B cells prevents lupus development in Sle lupus mice PKK deficiency in B cells prevents lupus development in Sle lupus mice](/preview/png/5666734.png)
- Lupus development in the Sle mouse model is blocked by B-cell specific PKK ablation.
- Multiple lupus-associated phenotypes are eliminated in PKK conditional knockout mice.
- Elevated BCR signaling seen in lupus mice is abrogated by PKK deficiency.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies that can result in damage to multiple organs. It is well documented that B cells play a critical role in the development of the disease. We previously showed that protein kinase C associated kinase (PKK) is required for B1 cell development as well as for the survival of recirculating mature B cells and B-lymphoma cells. Here, we investigated the role of PKK in lupus development in a lupus mouse model. We demonstrate that the conditional deletion of PKK in B cells prevents lupus development in Sle1Sle3 mice. The loss of PKK in Sle mice resulted in the amelioration of multiple classical lupus-associated phenotypes and histologic features of lupus nephritis, including marked reduction in the levels of serum autoantibodies, proteinuria, spleen size, peritoneal B-1 cell population and the number of activated CD4 T cells. In addition, the abundance of autoreactive plasma cells normally seen in Sle lupus mice was also significantly decreased in the PKK-deficient Sle mice. Sle B cells deficient in PKK display defective proliferation responses to BCR and LPS stimulation. Consistently, B cell receptor-mediated NF-κB activation, which is required for the survival of activated B cells, was impaired in the PKK-deficient B cells. Taken together, our work uncovers a critical role of PKK in lupus development and suggests that targeting the PKK-mediated pathway may represent a promising therapeutic strategy for lupus treatment.
Journal: Immunology Letters - Volume 185, May 2017, Pages 1-11