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Conference Paper: Lupus monocyte-derived dendritic cells treated with 1α,25-dihydroxyvitamin D3 and dexamethasone are tolerogenic and induce IL-10 producing regulatory T cells

TitleLupus monocyte-derived dendritic cells treated with 1α,25-dihydroxyvitamin D3 and dexamethasone are tolerogenic and induce IL-10 producing regulatory T cells
Authors
Issue Date2013
PublisherB M J Publishing Group. The Journal's web site is located at http://ard.bmjjournals.com/
Citation
The European League Against Rheumatism (EULAR) Congress, Madrid, Spain, 12-15 June 2013.In Annals of the Rheumatic Diseases: the EULAR journal, 2013, v. 72 n. Suppl. 3, p. 825. abstract no. AB0131 How to Cite?
AbstractBackground: The pathogenesis of systemic lupus erythematosus (SLE) is characterized by dysregulated dendritic cells (DCs) with over-production of type I interferon and hyperactive adaptive immune response. Clinical benefits of tolerogenic DCs have recently been shown in some murine models of immune mediated diseases. Objectives: To examine if alternatively activated DCs (aaDCs) derived from SLE patients possess tolerogenic properties and to delineate the underlying mechanisms. Methods: Lupus and healthy control aaDCs were generated by treating monocyte derived DCs using combination of 1α,25-Dihydroxyvitamin D3 (vitD3) and dexamethasone followed by maturation by lipopolysaccharide (LPS). These aaDCs were examined for phenotype and tolerogenic functions compared with LPS-matured DCs (matDCs). Activation markers and intracellular cytokine expression of T cells and/or DCs were measured by flow cytometry. ELISA was used to measure cytokine levels in supernatant. Western blot was performed for detection of RelB protein expression. Results: Compared with matDCs, lupus aaDCs displayed semi-mature phenotype with low level of expression of co-stimulatory molecules and maturation markers (CD83, CD40), that remained stable despite challenge by CD40L, CpG-DNA and SLE serum. These aaDCs also possessed tolerogenic phenotype with suppressive effect on allogeneic T cell activation (CD25 and CD69 expression) and proliferation comparable to normal aaDCs. Lupus and normal aaDCs were shown to polarize normal and lupus naïve CD45RA+ T cells into T effector cells that were characterized by production of high level of IL-10, expression of Foxp3 mRNA and antigen-nonspecific suppressive effect on allogeneic third-party T cells. On the other hand, lupus and normal aaDCs skewed memory CD45RO+ T cells to less inflammatory phenotype with reduced expression of IFN-γ and IL-17. Although aaDCs displayed a cytokine profile of IL-12loIL-10hi, addition of neutralizing anti-IL-12 and exogenous IL-10 to culture conditions did not reverse the suppressive effect of aaDCs on activation and proliferation of allogeneic T cells, suggesting their tolerogenicity cannot be accounted by cytokine imbalance between IL-12 and IL-10. On the other hand, aaDCs were found to express reduced level of RelB, a transcription factor regulating DC differentiation and maturation. Conclusions: Lupus aaDCs demonstrated tolerogenic properties with induction of IL-10 producing T cells that have regulatory functions. Reduced expression of RelB in aaDCs may be the underlying mechanism for their tolerogenicity. Disclosure of Interest: None Declared
DescriptionSession: SLE, Sjögren's and APS – etiology, pathogenesis and animal models
Persistent Identifierhttp://hdl.handle.net/10722/186811
ISSN
2015 Impact Factor: 12.384
2015 SCImago Journal Rankings: 4.537

 

DC FieldValueLanguage
dc.contributor.authorWu, Hen_US
dc.contributor.authorLuk, TWen_US
dc.contributor.authorLam, KYIen_US
dc.contributor.authorLau, WCSen_US
dc.contributor.authorChan, WKen_US
dc.contributor.authorMok, TMYen_US
dc.date.accessioned2013-08-20T12:21:07Z-
dc.date.available2013-08-20T12:21:07Z-
dc.date.issued2013en_US
dc.identifier.citationThe European League Against Rheumatism (EULAR) Congress, Madrid, Spain, 12-15 June 2013.In Annals of the Rheumatic Diseases: the EULAR journal, 2013, v. 72 n. Suppl. 3, p. 825. abstract no. AB0131en_US
dc.identifier.issn0003-4967-
dc.identifier.urihttp://hdl.handle.net/10722/186811-
dc.descriptionSession: SLE, Sjögren's and APS – etiology, pathogenesis and animal models-
dc.description.abstractBackground: The pathogenesis of systemic lupus erythematosus (SLE) is characterized by dysregulated dendritic cells (DCs) with over-production of type I interferon and hyperactive adaptive immune response. Clinical benefits of tolerogenic DCs have recently been shown in some murine models of immune mediated diseases. Objectives: To examine if alternatively activated DCs (aaDCs) derived from SLE patients possess tolerogenic properties and to delineate the underlying mechanisms. Methods: Lupus and healthy control aaDCs were generated by treating monocyte derived DCs using combination of 1α,25-Dihydroxyvitamin D3 (vitD3) and dexamethasone followed by maturation by lipopolysaccharide (LPS). These aaDCs were examined for phenotype and tolerogenic functions compared with LPS-matured DCs (matDCs). Activation markers and intracellular cytokine expression of T cells and/or DCs were measured by flow cytometry. ELISA was used to measure cytokine levels in supernatant. Western blot was performed for detection of RelB protein expression. Results: Compared with matDCs, lupus aaDCs displayed semi-mature phenotype with low level of expression of co-stimulatory molecules and maturation markers (CD83, CD40), that remained stable despite challenge by CD40L, CpG-DNA and SLE serum. These aaDCs also possessed tolerogenic phenotype with suppressive effect on allogeneic T cell activation (CD25 and CD69 expression) and proliferation comparable to normal aaDCs. Lupus and normal aaDCs were shown to polarize normal and lupus naïve CD45RA+ T cells into T effector cells that were characterized by production of high level of IL-10, expression of Foxp3 mRNA and antigen-nonspecific suppressive effect on allogeneic third-party T cells. On the other hand, lupus and normal aaDCs skewed memory CD45RO+ T cells to less inflammatory phenotype with reduced expression of IFN-γ and IL-17. Although aaDCs displayed a cytokine profile of IL-12loIL-10hi, addition of neutralizing anti-IL-12 and exogenous IL-10 to culture conditions did not reverse the suppressive effect of aaDCs on activation and proliferation of allogeneic T cells, suggesting their tolerogenicity cannot be accounted by cytokine imbalance between IL-12 and IL-10. On the other hand, aaDCs were found to express reduced level of RelB, a transcription factor regulating DC differentiation and maturation. Conclusions: Lupus aaDCs demonstrated tolerogenic properties with induction of IL-10 producing T cells that have regulatory functions. Reduced expression of RelB in aaDCs may be the underlying mechanism for their tolerogenicity. Disclosure of Interest: None Declared-
dc.languageengen_US
dc.publisherB M J Publishing Group. The Journal's web site is located at http://ard.bmjjournals.com/-
dc.relation.ispartofAnnals of the Rheumatic Diseases: the EULAR journalen_US
dc.rightsAnnals of the Rheumatic Diseases: the EULAR journal. Copyright © B M J Publishing Group.-
dc.titleLupus monocyte-derived dendritic cells treated with 1α,25-dihydroxyvitamin D3 and dexamethasone are tolerogenic and induce IL-10 producing regulatory T cellsen_US
dc.typeConference_Paperen_US
dc.identifier.emailLau, WCS: cslau@hku.hken_US
dc.identifier.emailChan, WK: wkchanf@hku.hken_US
dc.identifier.emailMok, TMY: temy@hkucc.hku.hken_US
dc.identifier.authorityLau, WCS=rp01348en_US
dc.identifier.authorityMok, TMY=rp00490en_US
dc.identifier.doi10.1136/annrheumdis-2013-eular.2454-
dc.identifier.hkuros217224en_US
dc.identifier.volume72en_US
dc.identifier.issueSuppl. 3en_US
dc.identifier.spage825. abstract no. AB0131en_US
dc.identifier.epage825. abstract no. AB0131en_US
dc.publisher.placeUnited Kingdom-

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