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Open Access Research article

Phenotypic and functional abnormalities of bone marrow-derived dendritic cells in systemic lupus erythematosus

Ying J Nie1, Mo Y Mok1, Godfrey CF Chan2, Albert W Chan1, Ou Jin1, Sushma Kavikondala1, Albert KW Lie1 and Chak S Lau1*

Author Affiliations

1 Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, PR China

2 Department of Paediatrics & Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, PR China

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Arthritis Research & Therapy 2010, 12:R91  doi:10.1186/ar3018

Published: 18 May 2010

Abstract

Introduction

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoreactive T and B cells, which are believed to be secondary to deficient dendritic cells (DCs). However, whether DC abnormalities occur during their development in the bone marrow (BM) or in the periphery is not known.

Methods

Thirteen patients with SLE and 16 normal controls were recruited. We studied the morphology, phenotype, and functional abilities of bone marrow-derived dendritic cells (BMDCs) generated by using two culture methods: FMS-like tyrosine kinase 3 (Flt3)-ligand (FL) and granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin-4 (IL-4), respectively.

Results

BMDCs induced by FL exhibited both myeloid (mDC) and plasmacytoid DC (pDC) features, whereas GM-CSF/IL-4 induced mDC generation. Substantial phenotypic and functional defects of BMDCs were found from patients with SLE at different stages of cell maturation. When compared with healthy controls, SLE immature BM FLDCs expressed higher levels of CCR7. Both immature and mature SLE BM FLDCs expressed higher levels of CD40 and CD86 and induced stronger T-cell proliferation. SLE BM mDCs expressed higher levels of CD40 and CD86 but lower levels of HLA-DR and a lower ability to stimulate T-cell proliferation when compared with control BM mDCs.

Conclusions

Our data are in accordance with previous reports that suggest that DCs have a potential pathogenic role in SLE. Defects of these cells are evident during their development in BM. BM mDCs are deficient, whereas BM pDCs, which are part of BM FLDCs, are the likely culprit in inducing autoimmunity in SLE.