Interleukin–21 is increased in active systemic lupus erythematosus patients and contributes to the generation of plasma B cells

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Rheumatology ArticleM. Nakou, E. Papadimitraki, A. Fanouriakis, G. Bertsias, C. Choulaki, N. Goulidaki, P. Sidiropoulos, D. Boumpas

Laboratory of Autoimmunity and Inflammation, Rheumatology, Clinical Immunology and Allergy, Medical School, University of Crete, and Institute for Molecular Biology and Biotechnology, FORTH, Greece. mnakou@hotmail.com

CER5206 Submission on line 2013 Vol.31, N°2 - PI 0172, PF 0179
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Excessive interleukin- (IL-) 21 production by T cells has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). We explored the expression and function of IL-21 in human SLE.
IL-21 and IL-21 receptor (IL-21R) expression was assessed by real-time PCR and flow cytometry in peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy controls. PBMCs, purified CD19+CD27– naïve and CD19+CD27+ memory B cells were stimulated with IL-21 and CpG-ODN2006 (TLR-9 agonist) to examine generation of memory and plasma (CD19+CD38highIgD–) B cells. Apoptosis was assessed by 7AAD staining.
Active SLE patients had 4-fold higher IL-21 mRNA and increased levels of intracellular IL-21 in peripheral blood CD4+ T cells (mean±SD fluorescence intensity, 1.7±0.1 in active versus 0.9±0.3 in inactive SLE and controls, p=0.035). IL-21R mRNA was comparable between SLE and healthy controls. Stimulation of PBMCs with IL-21 increased the proportion of memory and plasma cells; addition of CpG-ODN2006 enhanced these effects. Both naïve and memory B cells responded to IL-21/TLR-9 by increased generation of memory and plasma B cells, respectively; an anti-apoptotic effect was observed. In active SLE, PBMCs stimulation with IL-21 and/or CpG-ODN increased memory and plasma B cells, comparable to healthy controls. Addition of IL-21 to lupus autologous mixed lymphocyte cultures induced significant IgG production, and treatment with IL-21R.Fc to block IL-21/IL-21R interaction reduced the proportion of plasma cells.
Increased IL-21 may synergise with TLR-9 signalling and contributes to generation of plasma cells in active SLE patients.

PMID: 23137515 [PubMed]

Received: 28/10/2011 - Accepted : 14/05/2012 - In Press: 06/11/2012 - Published: 15/03/2013