Altered dendritic cells with tolerizing phenotype in patients with systemic lupus erythematosus

2008 ◽  
Vol 38 (10) ◽  
pp. 2896-2904 ◽  
Author(s):  
Yackov Berkun ◽  
Inna Verbovetski ◽  
Anat Ben-Ami ◽  
Daphna Paran ◽  
Dan Caspi ◽  
...  
2012 ◽  
Vol 71 (Suppl 1) ◽  
pp. A34.1-A34
Author(s):  
Ahsen Morva ◽  
Sébastien Lemoine ◽  
Achouak Achour ◽  
Alain Saraux ◽  
Jacques-Olivier Pers ◽  
...  

2015 ◽  
Vol 112 (45) ◽  
pp. E6195-E6204 ◽  
Author(s):  
Teja Celhar ◽  
Richard Hopkins ◽  
Susannah I. Thornhill ◽  
Raquel De Magalhaes ◽  
Sun-Hee Hwang ◽  
...  

Glomerulonephritis is a common and debilitating feature of systemic lupus erythematosus (SLE). The precise immune mechanisms that drive the progression from benign autoimmunity to glomerulonephritis are largely unknown. Previous investigations have shown that a moderate increase of the innate Toll-like receptor 7 (TLR7) is sufficient for the development of nephritis. In these systems normalization of B-cell TLR7 expression or temporal depletion of plasmacytoid dendritic cells (pDCs) slow progression; however, the critical cell that is responsible for driving full immunopathology remains unidentified. In this investigation we have shown that conventional DC expression of TLR7 is essential for severe autoimmunity in the Sle1Tg7 model of SLE. We show that a novel expanding CD11b+ conventional DC subpopulation dominates the infiltrating renal inflammatory milieu, localizing to the glomeruli. Moreover, exposure of human myeloid DCs to IFN-α or Flu increases TLR7 expression, suggesting they may have a role in self-RNA recognition pathways in clinical disease. To our knowledge, this study is the first to highlight the importance of conventional DC-TLR7 expression for kidney pathogenesis in a murine model of SLE.


2002 ◽  
Vol 63 (12) ◽  
pp. 1172-1180 ◽  
Author(s):  
Michelle A Gill ◽  
Patrick Blanco ◽  
Edsel Arce ◽  
Virginia Pascual ◽  
Jacques Banchereau ◽  
...  

Author(s):  
Anna Wardowska ◽  
Żaneta Smoleńska ◽  
Katarzyna A. Lisowska ◽  
Zbigniew Zdrojewski ◽  
Michał Pikuła

The systemic lupus erythematosus (SLE) is a chronic autoimmune disease related to a loss of immune tolerance against autoantigens that leads to tissue inflammation and organ dysfunction. Constant stimulation of dendritic cells (DC) with autoantigens is hypothesized to increase the B cells’ activity which are involved in production of autoantibodies that play an essential role in the SLE development. We focused our study on detecting alterations in DCs at the cellular and molecular levels in patients with treated SLE, depending on the disease activity and treatment. In order to phenotype subpopulations of DCs, multicolor flow cytometry was used. Transcriptional changes were identified with quantitative PCR, while soluble cytokine receptors were assessed with the Luminex technology. We show that SLE patients display a higher percentage of activated myeloid DCs (mDCs) when compared to healthy people. Both, the mDCs and plasmacytoid DCs (pDCs) of SLE patients were characterized by changes in expression of genes associated with their maturation, functioning and signalling, which was especially reflected by low expression of regulatory factor ID2 and increased expression of IRF5. pDCs of SLE patients also showed increased expression of IRF1. There were also significant changes in the expression of APRIL, MBD2, and E2-2 in mDCs that significantly correlated with some serum components, i.e. anti-dsDNA antibodies or complement components. However, we did not find any significant differences depending on the disease activity. While the majority of available studies focuses mainly on the role of pDCs in the disease development, our results show significant disturbances in the functioning of mDCs in SLE patients, thus confirming mDCs’ importance in SLE pathogenesis.


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