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- Publisher Website: 10.1016/j.clim.2008.06.004
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- PMID: 18684674
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Article: TLR9/TLR7-triggered downregulation of BDCA2 expression on human plasmacytoid dendritic cells from healthy individuals and lupus patients
Title | TLR9/TLR7-triggered downregulation of BDCA2 expression on human plasmacytoid dendritic cells from healthy individuals and lupus patients | ||||||||
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Authors | |||||||||
Keywords | BDCA2 Plasmacytoid dendritic cells Systemic lupus erythematosus TLR7 TLR9 | ||||||||
Issue Date | 2008 | ||||||||
Publisher | Academic Press. The Journal's web site is located at http://www.elsevier.com/locate/yclim | ||||||||
Citation | Clinical Immunology, 2008, v. 129 n. 1, p. 40-48 How to Cite? | ||||||||
Abstract | Plasmacytoid dendritic cells (pDCs) can produce a large amount of interferon-alpha (IFN-α) upon exposure to TLR9 or TLR7 agonists. Human pDCs have been shown to play an important role in the pathogenesis of systemic lupus erythematosus (SLE) through increased production of IFN-α. So, how to negatively regulate activation of pDCs and how to evaluate the activation of pDC in SLE patients attract much attention. BDCA2 is selectively expressed on human pDCs, acting as a hallmark of human pDCs. In this study, we showed that BDCA2 expression on pDCs decreased along maturation of pDCs, and TLR7 or TLR9 agonists could further significantly downregulate pDCs to express BDCA2, suggesting that the activated pDCs exhibit decreased expression of BDCA2. Functionally, BDCA2 ligation significantly inhibited upregulation of CD40, CD86 and CCR7 expression, IFN-α, IFN-β and IL-6 production by pDCs stimulated with CpG ODN. Moreover, BDCA2 ligation suppressed CpG ODN-activated pDCs to mediate Th1 response, including T cell proliferation, IFN-γ production, and CD4+CCR5+Th1 development, confirming that BDCA2 is a negative regulator of TLR9-dependent activation of human pDCs. BDCA2 expression on pDCs from SLE patients decreased significantly but IFN-α production of these patients increased markedly as compared to that from healthy donors. Therefore, these results suggest that downregulation of BDCA2 expression on pDCs may reflect the activation of pDCs accumulated in SLE patients, and may be one marker for indication of the disease activity of SLE patients. © 2008 Elsevier Inc. All rights reserved. | ||||||||
Persistent Identifier | http://hdl.handle.net/10722/60566 | ||||||||
ISSN | 2021 Impact Factor: 10.190 2020 SCImago Journal Rankings: 1.236 | ||||||||
ISI Accession Number ID |
Funding Information: We thank Prof. Xueguang Zhang from Suzhou University, PR China for kindly providing agonist anti-CD40 mAb (5C11), and Dr. Dennis M. Klinman from Food and Drug Administration, USA for kindly providing D-type CpG ODN. This work was supported by grants from the National Natural Science Foundation of China (30731160623, 30771985, 30490240, 30721091), the National Key Basic Research Program of China (2007CB512403) and Shanghai Committee of Science and Technology (05DZ22106). | ||||||||
References |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Wu, P | en_HK |
dc.contributor.author | Wu, J | en_HK |
dc.contributor.author | Liu, S | en_HK |
dc.contributor.author | Han, X | en_HK |
dc.contributor.author | Lu, J | en_HK |
dc.contributor.author | Shi, Y | en_HK |
dc.contributor.author | Wang, J | en_HK |
dc.contributor.author | Lu, L | en_HK |
dc.contributor.author | Cao, X | en_HK |
dc.date.accessioned | 2010-05-31T04:13:48Z | - |
dc.date.available | 2010-05-31T04:13:48Z | - |
dc.date.issued | 2008 | en_HK |
dc.identifier.citation | Clinical Immunology, 2008, v. 129 n. 1, p. 40-48 | en_HK |
dc.identifier.issn | 1521-6616 | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/60566 | - |
dc.description.abstract | Plasmacytoid dendritic cells (pDCs) can produce a large amount of interferon-alpha (IFN-α) upon exposure to TLR9 or TLR7 agonists. Human pDCs have been shown to play an important role in the pathogenesis of systemic lupus erythematosus (SLE) through increased production of IFN-α. So, how to negatively regulate activation of pDCs and how to evaluate the activation of pDC in SLE patients attract much attention. BDCA2 is selectively expressed on human pDCs, acting as a hallmark of human pDCs. In this study, we showed that BDCA2 expression on pDCs decreased along maturation of pDCs, and TLR7 or TLR9 agonists could further significantly downregulate pDCs to express BDCA2, suggesting that the activated pDCs exhibit decreased expression of BDCA2. Functionally, BDCA2 ligation significantly inhibited upregulation of CD40, CD86 and CCR7 expression, IFN-α, IFN-β and IL-6 production by pDCs stimulated with CpG ODN. Moreover, BDCA2 ligation suppressed CpG ODN-activated pDCs to mediate Th1 response, including T cell proliferation, IFN-γ production, and CD4+CCR5+Th1 development, confirming that BDCA2 is a negative regulator of TLR9-dependent activation of human pDCs. BDCA2 expression on pDCs from SLE patients decreased significantly but IFN-α production of these patients increased markedly as compared to that from healthy donors. Therefore, these results suggest that downregulation of BDCA2 expression on pDCs may reflect the activation of pDCs accumulated in SLE patients, and may be one marker for indication of the disease activity of SLE patients. © 2008 Elsevier Inc. All rights reserved. | en_HK |
dc.language | eng | en_HK |
dc.publisher | Academic Press. The Journal's web site is located at http://www.elsevier.com/locate/yclim | en_HK |
dc.relation.ispartof | Clinical Immunology | en_HK |
dc.subject | BDCA2 | - |
dc.subject | Plasmacytoid dendritic cells | - |
dc.subject | Systemic lupus erythematosus | - |
dc.subject | TLR7 | - |
dc.subject | TLR9 | - |
dc.subject.mesh | Antigen-Antibody Complex - blood | en_HK |
dc.subject.mesh | Cytokines - immunology - metabolism | en_HK |
dc.subject.mesh | Dendritic Cells - immunology - metabolism | en_HK |
dc.subject.mesh | Down-Regulation | en_HK |
dc.subject.mesh | Humans | en_HK |
dc.subject.mesh | Lectins, C-Type - immunology - metabolism | en_HK |
dc.subject.mesh | Lupus Erythematosus, Systemic - immunology - metabolism | en_HK |
dc.subject.mesh | Membrane Glycoproteins - immunology - metabolism | en_HK |
dc.subject.mesh | Oligodeoxyribonucleotides - immunology | en_HK |
dc.subject.mesh | Receptors, Immunologic - immunology - metabolism | en_HK |
dc.subject.mesh | Th1 Cells - immunology - metabolism | en_HK |
dc.subject.mesh | Th2 Cells - immunology - metabolism | en_HK |
dc.subject.mesh | Toll-Like Receptor 7 - immunology - metabolism | en_HK |
dc.subject.mesh | Toll-Like Receptor 9 - immunology - metabolism | en_HK |
dc.subject.mesh | Up-Regulation | en_HK |
dc.title | TLR9/TLR7-triggered downregulation of BDCA2 expression on human plasmacytoid dendritic cells from healthy individuals and lupus patients | en_HK |
dc.type | Article | en_HK |
dc.identifier.openurl | http://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1521-6616&volume=129&issue=1&spage=40&epage=8&date=2008&atitle=TLR9/TLR7-triggered+downregulation+of+BDCA2+expression+on+human+plasmacytoid+dendritic+cells+from+healthy+individuals+and+lupus+patients. | en_HK |
dc.identifier.email | Lu, L:liweilu@hkucc.hku.hk | en_HK |
dc.identifier.authority | Lu, L=rp00477 | en_HK |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1016/j.clim.2008.06.004 | en_HK |
dc.identifier.pmid | 18684674 | - |
dc.identifier.scopus | eid_2-s2.0-51249104878 | en_HK |
dc.identifier.hkuros | 162557 | en_HK |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-51249104878&selection=ref&src=s&origin=recordpage | en_HK |
dc.identifier.volume | 129 | en_HK |
dc.identifier.issue | 1 | en_HK |
dc.identifier.spage | 40 | en_HK |
dc.identifier.epage | 48 | en_HK |
dc.identifier.isi | WOS:000259459200007 | - |
dc.publisher.place | United States | en_HK |
dc.identifier.issnl | 1521-6616 | - |