File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Conference Paper: Bone marrow derived dendritic cells modified by lentiviral-mediated RelB shRNA possess tolerogenic phenotype and functions on lupus splenic lymphocytes

TitleBone marrow derived dendritic cells modified by lentiviral-mediated RelB shRNA possess tolerogenic phenotype and functions on lupus splenic lymphocytes
Authors
Issue Date2015
PublisherBMJ Publishing Group. The Journal's web site is located at http://ard.bmjjournals.com/
Citation
16th Annual European Congress of Rheumatology - European League Against Rheumatism (EULAR), Rome, Italy, 10-13 June 2015. In Annals of the Rheumatic Diseases, 2015, v. 74 n. Suppl. 2, p. 951, abstract no. AB0181 How to Cite?
AbstractBackground Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by high morbidity and mortality and remains challenging in treatment. Dendritic cells (DCs) have been shown to participate in the initiation and perpetuation of lupus pathogenesis. DCs that induce tolerogenicity appear as potential cell-based therapy in this condition. Objectives In this study, we used lentiviral transduction of RelB-silencing shRNA to modify expression of RelB, a key transcription factor regulating DC maturation, in bone marrow-derived DCs from MRL/MpJ wild type mice and examined their tolerogenic properties using a lupus-prone MRL/lpr model. Methods Lentiviral-mediated transduction of RelB-silencing shRNA or scrambled control shRNA were used to treat bone marrow derived DCs from MRL/MpJ mice. LPS-matured DCs, scrambled shRNA-modified DCs and RelB-modiified DCs were compared in terms of their tolerogenic properties. Results We found that these MRL/MpJ RelB-modified DCs displayed semi-mature phenotype. These MRL/MpJ RelB-modified DCs were found to be low producer of IL-12p70, can induce hyporesponsiveness of splenic T cells from MRL/MpJ and lupus-prone MRL/lpr mice. Furthermore, they downregulated IFN-γ expression and induced IL-10 producing T cells in MRL/MpJ splenocytes, and attenuated IFN-γ and IL-17 expression in MRL/lpr splenic lymphocytes. Splenocytes primed by RelB-modified DCs demonstrated antigen-specific suppressive effect on allogeneic splenocytes. However, these CD4+ T cells with suppressive function were not found to express Foxp3. In the terms of chemokine receptor expression, there were no differences in the expression of CCR5, CCR7, and CXCR3 bewteen RelB- and scrambled control-modified DCs. Conclusions RelB-modified DCs provide a method in the generation of tolerogenic DCs which may have potential therapeutic implications in the treatment of SLE.
Persistent Identifierhttp://hdl.handle.net/10722/218979
ISSN
2015 Impact Factor: 12.384
2015 SCImago Journal Rankings: 4.537

 

DC FieldValueLanguage
dc.contributor.authorWu, HJ-
dc.contributor.authorLo, Y-
dc.contributor.authorChan, WK-
dc.contributor.authorMok, TMY-
dc.date.accessioned2015-09-18T07:02:46Z-
dc.date.available2015-09-18T07:02:46Z-
dc.date.issued2015-
dc.identifier.citation16th Annual European Congress of Rheumatology - European League Against Rheumatism (EULAR), Rome, Italy, 10-13 June 2015. In Annals of the Rheumatic Diseases, 2015, v. 74 n. Suppl. 2, p. 951, abstract no. AB0181-
dc.identifier.issn0003-4967-
dc.identifier.urihttp://hdl.handle.net/10722/218979-
dc.description.abstractBackground Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by high morbidity and mortality and remains challenging in treatment. Dendritic cells (DCs) have been shown to participate in the initiation and perpetuation of lupus pathogenesis. DCs that induce tolerogenicity appear as potential cell-based therapy in this condition. Objectives In this study, we used lentiviral transduction of RelB-silencing shRNA to modify expression of RelB, a key transcription factor regulating DC maturation, in bone marrow-derived DCs from MRL/MpJ wild type mice and examined their tolerogenic properties using a lupus-prone MRL/lpr model. Methods Lentiviral-mediated transduction of RelB-silencing shRNA or scrambled control shRNA were used to treat bone marrow derived DCs from MRL/MpJ mice. LPS-matured DCs, scrambled shRNA-modified DCs and RelB-modiified DCs were compared in terms of their tolerogenic properties. Results We found that these MRL/MpJ RelB-modified DCs displayed semi-mature phenotype. These MRL/MpJ RelB-modified DCs were found to be low producer of IL-12p70, can induce hyporesponsiveness of splenic T cells from MRL/MpJ and lupus-prone MRL/lpr mice. Furthermore, they downregulated IFN-γ expression and induced IL-10 producing T cells in MRL/MpJ splenocytes, and attenuated IFN-γ and IL-17 expression in MRL/lpr splenic lymphocytes. Splenocytes primed by RelB-modified DCs demonstrated antigen-specific suppressive effect on allogeneic splenocytes. However, these CD4+ T cells with suppressive function were not found to express Foxp3. In the terms of chemokine receptor expression, there were no differences in the expression of CCR5, CCR7, and CXCR3 bewteen RelB- and scrambled control-modified DCs. Conclusions RelB-modified DCs provide a method in the generation of tolerogenic DCs which may have potential therapeutic implications in the treatment of SLE.-
dc.languageeng-
dc.publisherBMJ Publishing Group. The Journal's web site is located at http://ard.bmjjournals.com/-
dc.relation.ispartofAnnals of the Rheumatic Diseases-
dc.rightsAnnals of the Rheumatic Diseases. Copyright © BMJ Publishing Group.-
dc.titleBone marrow derived dendritic cells modified by lentiviral-mediated RelB shRNA possess tolerogenic phenotype and functions on lupus splenic lymphocytes-
dc.typeConference_Paper-
dc.identifier.emailLo, Y: yloa@hkucc.hku.hk-
dc.identifier.emailChan, WK: wkchanf@hku.hk-
dc.identifier.emailMok, TMY: temy@hkucc.hku.hk-
dc.identifier.authorityMok, TMY=rp00490-
dc.identifier.doi10.1136/annrheumdis-2015-eular.2462-
dc.identifier.hkuros253045-
dc.identifier.volume74-
dc.identifier.issueSuppl. 2-
dc.identifier.spage951-
dc.identifier.epage951-
dc.publisher.placeUnited Kingdom-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats