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Article: TLR9/TLR7-triggered downregulation of BDCA2 expression on human plasmacytoid dendritic cells from healthy individuals and lupus patients

TitleTLR9/TLR7-triggered downregulation of BDCA2 expression on human plasmacytoid dendritic cells from healthy individuals and lupus patients
Authors
Issue Date2008
PublisherAcademic 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?
AbstractPlasmacytoid 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 Identifierhttp://hdl.handle.net/10722/60566
ISSN
2015 Impact Factor: 4.034
2015 SCImago Journal Rankings: 1.848
ISI Accession Number ID
Funding AgencyGrant Number
National Natural Science Foundation of China30731160623
30771985
30490240
30721091
National Key Basic Research Program of China2007CB512403
Shanghai Committee of Science and Technology05DZ22106
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 FieldValueLanguage
dc.contributor.authorWu, Pen_HK
dc.contributor.authorWu, Jen_HK
dc.contributor.authorLiu, Sen_HK
dc.contributor.authorHan, Xen_HK
dc.contributor.authorLu, Jen_HK
dc.contributor.authorShi, Yen_HK
dc.contributor.authorWang, Jen_HK
dc.contributor.authorLu, Len_HK
dc.contributor.authorCao, Xen_HK
dc.date.accessioned2010-05-31T04:13:48Z-
dc.date.available2010-05-31T04:13:48Z-
dc.date.issued2008en_HK
dc.identifier.citationClinical Immunology, 2008, v. 129 n. 1, p. 40-48en_HK
dc.identifier.issn1521-6616en_HK
dc.identifier.urihttp://hdl.handle.net/10722/60566-
dc.description.abstractPlasmacytoid 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.languageengen_HK
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yclimen_HK
dc.relation.ispartofClinical Immunologyen_HK
dc.subject.meshAntigen-Antibody Complex - blooden_HK
dc.subject.meshCytokines - immunology - metabolismen_HK
dc.subject.meshDendritic Cells - immunology - metabolismen_HK
dc.subject.meshDown-Regulationen_HK
dc.subject.meshHumansen_HK
dc.subject.meshLectins, C-Type - immunology - metabolismen_HK
dc.subject.meshLupus Erythematosus, Systemic - immunology - metabolismen_HK
dc.subject.meshMembrane Glycoproteins - immunology - metabolismen_HK
dc.subject.meshOligodeoxyribonucleotides - immunologyen_HK
dc.subject.meshReceptors, Immunologic - immunology - metabolismen_HK
dc.subject.meshTh1 Cells - immunology - metabolismen_HK
dc.subject.meshTh2 Cells - immunology - metabolismen_HK
dc.subject.meshToll-Like Receptor 7 - immunology - metabolismen_HK
dc.subject.meshToll-Like Receptor 9 - immunology - metabolismen_HK
dc.subject.meshUp-Regulationen_HK
dc.titleTLR9/TLR7-triggered downregulation of BDCA2 expression on human plasmacytoid dendritic cells from healthy individuals and lupus patientsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://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.emailLu, L:liweilu@hkucc.hku.hken_HK
dc.identifier.authorityLu, L=rp00477en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.clim.2008.06.004en_HK
dc.identifier.pmid18684674-
dc.identifier.scopuseid_2-s2.0-51249104878en_HK
dc.identifier.hkuros162557en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-51249104878&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume129en_HK
dc.identifier.issue1en_HK
dc.identifier.spage40en_HK
dc.identifier.epage48en_HK
dc.identifier.isiWOS:000259459200007-
dc.publisher.placeUnited Statesen_HK

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