PMID- 20618924
OWN - NLM
STAT- MEDLINE
DCOM- 20110119
LR  - 20211020
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 12
IP  - 4
DP  - 2010
TI  - Abnormalities in circulating plasmacytoid dendritic cells in patients with 
      systemic lupus erythematosus.
PG  - R137
LID - 10.1186/ar3075 [doi]
AB  - INTRODUCTION: 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.
FAU - Jin, Ou
AU  - Jin O
AD  - Department of Medicine, The University of Hong Kong, Hong Kong, People's Republic 
      of China. jinouwishugood@hotmail.com
FAU - Kavikondala, Sushma
AU  - Kavikondala S
FAU - Mok, Mo-Yin
AU  - Mok MY
FAU - Sun, Lingyun
AU  - Sun L
FAU - Gu, Jieruo
AU  - Gu J
FAU - Fu, Rong
AU  - Fu R
FAU - Chan, Albert
AU  - Chan A
FAU - Yeung, Joseph
AU  - Yeung J
FAU - Nie, Yingjie
AU  - Nie Y
FAU - Lau, Chak-Sing
AU  - Lau CS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100709
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (Avian Proteins)
RN  - 0 (Cytokines)
RN  - 0 (EMF-1 protein, Gallus gallus)
RN  - 0 (FOXP3 protein, human)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (IL2RA protein, human)
RN  - 0 (Interleukin-2 Receptor alpha Subunit)
RN  - 0 (TLR9 protein, human)
RN  - 0 (Toll-Like Receptor 9)
SB  - IM
CIN - Nat Rev Rheumatol. 2010 Oct;6(10):553. PMID: 20925148
MH  - Adult
MH  - Avian Proteins/metabolism
MH  - Cell Division/immunology
MH  - Cytokines/metabolism
MH  - Dendritic Cells/*immunology/metabolism/*pathology
MH  - Female
MH  - Forkhead Transcription Factors/genetics
MH  - Gene Expression/immunology
MH  - Humans
MH  - Interleukin-2 Receptor alpha Subunit/genetics
MH  - Lupus Erythematosus, Systemic/*immunology/*pathology
MH  - Male
MH  - Middle Aged
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - T-Lymphocytes, Regulatory/immunology/pathology
MH  - Toll-Like Receptor 9/genetics/immunology
MH  - Young Adult
PMC - PMC2945027
EDAT- 2010/07/14 06:00
MHDA- 2011/01/20 06:00
PMCR- 2010/07/09
CRDT- 2010/07/13 06:00
PHST- 2009/10/13 00:00 [received]
PHST- 2010/05/12 00:00 [revised]
PHST- 2010/07/09 00:00 [accepted]
PHST- 2010/07/13 06:00 [entrez]
PHST- 2010/07/14 06:00 [pubmed]
PHST- 2011/01/20 06:00 [medline]
PHST- 2010/07/09 00:00 [pmc-release]
AID - ar3075 [pii]
AID - 10.1186/ar3075 [doi]
PST - ppublish
SO  - Arthritis Res Ther. 2010;12(4):R137. doi: 10.1186/ar3075. Epub 2010 Jul 9.