title: Abnormalities in circulating plasmacytoid dendritic cells in patients with systemic lupus erythematosus.
abstract: BACKGROUND
  Dendritic cells (DCs) are capable of inducing immunity or tolerance. Previous studies have suggested plasmacytoid DCs (pDCs) are pathogenic in systemic lupus erythematosus (SLE). However, the functional characteristics of directly isolated peripheral circulating blood pDCs in SLE have not been evaluated previously.
  
  
  METHODS
  Peripheral blood pDCs from 62 healthy subjects and 58 SLE patients were treated with apoptotic cells derived from polymorphonuclear cells (PMNs). Antigen loaded or unloaded pDCs were then co-cultured with autologous or allogenous T cells. Changes in T cell proliferation, cell surface CD25 expression, intracellular Foxp3 expression and cytokine production were evaluated. pDCs that had captured apoptotic PMNs (pDCs + apoPMNs were also studied for their cytokine production (interferon (IFN)-alpha, interleukin (IL)-6, IL-10, IL-18) and toll like receptor (TLR) expression.
  
  
  RESULTS
  Circulating pDCs from SLE patients had an increased ability to stimulate T cells when compared with control pDCs. Using allogenous T cells as responder cells, SLE pDCs induced T cell proliferation even in the absence of apoptotic PMNs. In addition, healthy pDCs + apoPMNs induced suppressive T regulatory cell features with increased Foxp3 expression in CD4 + CD25 + cells while SLE pDCs + apoPMNs did not. There were differences in the cytokine profile of pDCs that had captured apoptotic PMNs between healthy subjects and patients with SLE. Healthy pDCs + apoPMNs showed decreased production of IL-6 but no significant changes in IL-10 and IL-18. These pDCs + apoPMNs also showed increased mRNA transcription of TLR9. On the other hand, while SLE pDCs + apoPMNs also had decreased IL-6, there was decreased IL-18 mRNA expression and persistent IL-10 protein synthesis. In addition, SLE pDCs lacked TLR9 recruitment.
  
  
  CONCLUSIONS
  We have demonstrated that peripheral circulating pDCs in patients with SLE were functionally abnormal. They lacked TLR9 expression, were less capable of inducing regulatory T cell differentiation and had persistent IL-10 mRNA expression following the capture of apoptotic PMNs. We suggest circulating pDCs may be pathogenically relevant in SLE.
authors.affiliation: Department of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China. jinouwishugood@hotmail.com
authors.forename: Ou
authors.initials: O
authors.lastname: Jin
authors.forename: Sushma
authors.initials: S
authors.lastname: Kavikondala
authors.forename: Mo-Yin
authors.initials: MY
authors.lastname: Mok
authors.forename: Lingyun
authors.initials: L
authors.lastname: Sun
authors.forename: Jieruo
authors.initials: J
authors.lastname: Gu
authors.forename: Rong
authors.initials: R
authors.lastname: Fu
authors.forename: Albert
authors.initials: A
authors.lastname: Chan
authors.forename: Joseph
authors.initials: J
authors.lastname: Yeung
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Nie
authors.forename: Chak-Sing
authors.initials: CS
authors.lastname: Lau
mesh_terms: D000328:Adult; D030161:Avian Proteins / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D030161:Avian Proteins; D016207:Cytokines; C071280:EMF-1 protein, Gallus gallus; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9