Phenotypic and functional abnormalities of bone marrow-derived dendritic cells in systemic lupus erythematosus.
BACKGROUND
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.
Nie
Ying J
YJ
Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, PR China.
Mok
Mo Y
MY
Chan
Godfrey C F
GC
Chan
Albert W
AW
Jin
O U
OU
Kavikondala
Sushma
S
Lie
Albert K W
AK
Lau
Chak S
CS
D000328:Adult; D051940:B7-2 Antigen / Q000378:metabolism; D001854:Bone Marrow Cells / Q000473:pathology*; D019013:CD40 Antigens / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000473:pathology* / Q000502:physiology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D008565:Membrane Proteins / Q000494:pharmacology; D008875:Middle Aged; D010641:Phenotype; D054400:Receptors, CCR7 / Q000378:metabolism
D051940:B7-2 Antigen; C515370:CCR7 protein, human; D019013:CD40 Antigens; D016898:Interferon-alpha; D008565:Membrane Proteins; D054400:Receptors, CCR7; C084881:flt3 ligand protein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor