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Article: Heightened TLR7/9-Induced IL-10 and CXCL13 Production with Dysregulated NF-ҝB Activation in CD11chiCD11b+ Dendritic Cells in NZB/W F1 Mice

TitleHeightened TLR7/9-Induced IL-10 and CXCL13 Production with Dysregulated NF-ҝB Activation in CD11chiCD11b+ Dendritic Cells in NZB/W F1 Mice
Authors
Keywordssystemic lupus erythematosus
myeloid dendritic cell
Toll-like receptor 7
Toll-like receptor 9
interleukin 10
Issue Date2019
PublisherMolecular Diversity Preservation International. The Journal's web site is located at http://www.mdpi.org/ijms
Citation
International Journal of Molecular Sciences, 2019, v. 20 n. 18, p. article no. 4639 How to Cite?
AbstractSystemic lupus erythematosus (SLE) is a chronic, multifactorial autoimmune disease that predominantly affects young females. Dysregulation of different immune cell populations leads to self-tolerance breakdown and subsequent multiple organ damage as the disease develops. Plasmacytoid dendritic cells (pDCs) are potent producers of type I interferon (IFN), while myeloid dendritic cells (mDCs) are more specialized in antigen presentations. We have previously reported that bone-marrow (BM)-derived pDCs from the murine lupus model New Zealand black/white F1 (BWF1) possess abnormalities. Therefore, this study continues to investigate what aberrant properties peripheral pDCs and mDCs possess in BWF1 and how they mediate SLE progression, by comparing their properties in pre-symptomatic and symptomatic mice. Results showed that CD11chiCD11b+ myeloid DCs expanded during the disease state with down-regulation of co-stimulatory molecules and major histocompatibility complex class II molecules (MHC II), but their capacity to stimulate T cells was not hampered. During the disease state, this subset of mDCs displayed heightened toll-like receptors 7 and 9 (TLR 7/9) responses with increased interleukin 10 (IL-10) and C-X-C motif chemokine ligand 13 (CXCL13) expressions. Moreover, the expressions of myeloid differentiation primary response 88 (Myd88) and nuclear factor kappa B subunit 1 (Nfkb1) were higher in CD11chiCD11b+ DCs at the disease stage, leading to higher nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 phosphorylation activity. In summary, we reported aberrant phenotypic properties with enhanced TLR7/9 responses of CD11chiCD11b+ DCs in SLE mediated by aberrant NF-κB signaling pathway. Our findings add additional and novel information to our current understanding of the role of DCs in lupus immunopathogenesis. Lastly, molecular candidates in the NF-κB pathway should be exploited for developing therapeutic targets for SLE.
Persistent Identifierhttp://hdl.handle.net/10722/278215
ISSN
2011 Impact Factor: 2.598
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorYim, LY-
dc.contributor.authorLau, CS-
dc.contributor.authorChan, VSF-
dc.date.accessioned2019-10-04T08:09:42Z-
dc.date.available2019-10-04T08:09:42Z-
dc.date.issued2019-
dc.identifier.citationInternational Journal of Molecular Sciences, 2019, v. 20 n. 18, p. article no. 4639-
dc.identifier.issn1661-6596-
dc.identifier.urihttp://hdl.handle.net/10722/278215-
dc.description.abstractSystemic lupus erythematosus (SLE) is a chronic, multifactorial autoimmune disease that predominantly affects young females. Dysregulation of different immune cell populations leads to self-tolerance breakdown and subsequent multiple organ damage as the disease develops. Plasmacytoid dendritic cells (pDCs) are potent producers of type I interferon (IFN), while myeloid dendritic cells (mDCs) are more specialized in antigen presentations. We have previously reported that bone-marrow (BM)-derived pDCs from the murine lupus model New Zealand black/white F1 (BWF1) possess abnormalities. Therefore, this study continues to investigate what aberrant properties peripheral pDCs and mDCs possess in BWF1 and how they mediate SLE progression, by comparing their properties in pre-symptomatic and symptomatic mice. Results showed that CD11chiCD11b+ myeloid DCs expanded during the disease state with down-regulation of co-stimulatory molecules and major histocompatibility complex class II molecules (MHC II), but their capacity to stimulate T cells was not hampered. During the disease state, this subset of mDCs displayed heightened toll-like receptors 7 and 9 (TLR 7/9) responses with increased interleukin 10 (IL-10) and C-X-C motif chemokine ligand 13 (CXCL13) expressions. Moreover, the expressions of myeloid differentiation primary response 88 (Myd88) and nuclear factor kappa B subunit 1 (Nfkb1) were higher in CD11chiCD11b+ DCs at the disease stage, leading to higher nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 phosphorylation activity. In summary, we reported aberrant phenotypic properties with enhanced TLR7/9 responses of CD11chiCD11b+ DCs in SLE mediated by aberrant NF-κB signaling pathway. Our findings add additional and novel information to our current understanding of the role of DCs in lupus immunopathogenesis. Lastly, molecular candidates in the NF-κB pathway should be exploited for developing therapeutic targets for SLE.-
dc.languageeng-
dc.publisherMolecular Diversity Preservation International. The Journal's web site is located at http://www.mdpi.org/ijms-
dc.relation.ispartofInternational Journal of Molecular Sciences-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectsystemic lupus erythematosus-
dc.subjectmyeloid dendritic cell-
dc.subjectToll-like receptor 7-
dc.subjectToll-like receptor 9-
dc.subjectinterleukin 10-
dc.titleHeightened TLR7/9-Induced IL-10 and CXCL13 Production with Dysregulated NF-ҝB Activation in CD11chiCD11b+ Dendritic Cells in NZB/W F1 Mice-
dc.typeArticle-
dc.identifier.emailYim, LY: ayim@hku.hk-
dc.identifier.emailLau, CS: cslau@hku.hk-
dc.identifier.emailChan, VSF: sfvchan@hku.hk-
dc.identifier.authorityLau, CS=rp01348-
dc.identifier.authorityChan, VSF=rp01459-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3390/ijms20184639-
dc.identifier.pmid31546763-
dc.identifier.pmcidPMC6770860-
dc.identifier.scopuseid_2-s2.0-85072585759-
dc.identifier.hkuros306253-
dc.identifier.volume20-
dc.identifier.issue18-
dc.identifier.spagearticle no. 4639-
dc.identifier.epagearticle no. 4639-
dc.publisher.placeSwitzerland-

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