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122 Dendritic cells display aberrant toll-like receptor 7/9 responses in systemic lupus erythematosus
  1. A.L.Y Yim,
  2. S Yan,
  3. A Chan,
  4. VSF Chan and
  5. CS Lau
  1. LKS Faculty of Medicine- The University of Hong Kong, Department of Medicine, Hong Kong, Hong Kong S.A.R

Abstract

Background and aims Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease that causes multi-organ damages. Plasmacytoid dendritic cells (pDCs) are potent type I interferon (IFN) producers and myeloid dendritic cells (mDCs) are professional antigen presenting cells. Clinically, serum IFN-alpha (IFNa) level correlates with disease severity and mDCs from patients also display activated phenotypes. These observations suggested that different DCs subsets may mediate SLE pathogenesis. Therefore, the aim of this study was to evaluate whether pDCs and mDCs possessed aberrant properties that might mediate SLE progression.

Methods The properties of DCs from the murine lupus model New Zealand Black/White F1 (BWF1) were evaluated using flow cytometry, ELISA and qPCR.

Results Splenic pDCs abundance was similar before and after disease onset. The induction of CD40, CD80 and MHC II on pDCs upon Toll-like receptor (TLR) 7 or TLR9 stimulation and the level of IFN-alpha produced by pDCs in symptomatic and pre-symptomatic mice was also comparable. In contrast, splenic mDCs expanded in symptomatic mice. These mDCs decreased CD80 and MHC II expression but their ability in stimulating allogenic T cell proliferation was similar to mDCs from pre-symptomatic mice. On the other hand, TLR7 and TLR9 expressions in BWF1 mDCs were higher than mDCs from age- and sex-matched parental NZW controls. The amount of IL-10 and CXCL13 produced by mDCs from symptomatic mice upon TLR7 or TLR9 stimulation was also higher than its pre-symptomatic counterparts.

Conclusions Myeloid DCs displayed heightened TLR7 and TLR9 responses in SLE. More work is needed to further dissect how mDCs promote SLE pathogenesis.

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