PKK deficiency in B cells prevents lupus development in Sle lupus mice

D. Oleksyn, J. Zhao, A. Vosoughi, J. C. Zhao, R. Misra, A. P. Pentland, D. Ryan, J. Anolik, C. Ritchlin, J. Looney, A. P. Anandarajah, G. Schwartz, L. M. Calvi, M. Georger, C. Mohan, I. Sanz, L. Chen

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2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalImmunology Letters
Volume185
DOIs
StatePublished - May 1 2017

Keywords

  • BCR
  • Lupus
  • Mouse model
  • PKK

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Oleksyn, D., Zhao, J., Vosoughi, A., Zhao, J. C., Misra, R., Pentland, A. P., Ryan, D., Anolik, J., Ritchlin, C., Looney, J., Anandarajah, A. P., Schwartz, G., Calvi, L. M., Georger, M., Mohan, C., Sanz, I., & Chen, L. (2017). PKK deficiency in B cells prevents lupus development in Sle lupus mice. Immunology Letters, 185, 1-11. https://doi.org/10.1016/j.imlet.2017.03.002