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Article: TLR agonists downregulate H2-O in CD8a- dendritic cells

TitleTLR agonists downregulate H2-O in CD8a- dendritic cells
Authors
Issue Date2011
PublisherAmerican Association of Immunologists. The Journal's web site is located at http://www.jimmunol.org
Citation
Journal of Immunology, 2011, v. 187 n. 8, p. 4151-4160 How to Cite?
AbstractPeptide loading of MHC class II (MHCII) molecules is catalyzed by the nonclassical MHCII-related molecule H2-M. H2-O, another MHCII-like molecule, associates with H2-M and modulates H2-M function. The MHCII presentation pathway is tightly regulated in dendritic cells (DCs), yet how the key modulators of MHCII presentation, H2-M and H2-O, are affected in different DC subsets in response to maturation is unknown. In this study, we show that H2-O is markedly downregulated in vivo in mouse CD8α(-) DCs in response to a broad array of TLR agonists. In contrast, CD8α(+) DCs only modestly downregulated H2-O in response to TLR agonists. H2-M levels were slightly downmodulated in both CD8α(-) and CD8α(+) DCs. As a consequence, H2-M/H2-O ratios significantly increased for CD8α(-) but not for CD8α(+) DCs. The TLR-mediated downregulation was DC specific, as B cells did not show significant H2-O and H2-M downregulation. TLR4 signaling was required to mediate DC H2-O downregulation in response to LPS. Finally, our studies showed that the mechanism of H2-O downregulation was likely due to direct protein degradation of H2-O as well as downregulation of H2-O mRNA levels. The differential H2-O and H2-M modulation after DC maturation supports the proposed roles of CD8α(-) DCs in initiating CD4-restricted immune responses by optimal MHCII presentation and of CD8α(+) DCs in promoting immune tolerance via presentation of low levels of MHCII-peptide.
Persistent Identifierhttp://hdl.handle.net/10722/209257
ISSN
2015 Impact Factor: 4.985
2015 SCImago Journal Rankings: 3.549
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorPorter, GW-
dc.contributor.authorYi, WS-
dc.contributor.authorDenzin, LK-
dc.date.accessioned2015-04-14T06:08:18Z-
dc.date.available2015-04-14T06:08:18Z-
dc.date.issued2011-
dc.identifier.citationJournal of Immunology, 2011, v. 187 n. 8, p. 4151-4160-
dc.identifier.issn0022-1767-
dc.identifier.urihttp://hdl.handle.net/10722/209257-
dc.description.abstractPeptide loading of MHC class II (MHCII) molecules is catalyzed by the nonclassical MHCII-related molecule H2-M. H2-O, another MHCII-like molecule, associates with H2-M and modulates H2-M function. The MHCII presentation pathway is tightly regulated in dendritic cells (DCs), yet how the key modulators of MHCII presentation, H2-M and H2-O, are affected in different DC subsets in response to maturation is unknown. In this study, we show that H2-O is markedly downregulated in vivo in mouse CD8α(-) DCs in response to a broad array of TLR agonists. In contrast, CD8α(+) DCs only modestly downregulated H2-O in response to TLR agonists. H2-M levels were slightly downmodulated in both CD8α(-) and CD8α(+) DCs. As a consequence, H2-M/H2-O ratios significantly increased for CD8α(-) but not for CD8α(+) DCs. The TLR-mediated downregulation was DC specific, as B cells did not show significant H2-O and H2-M downregulation. TLR4 signaling was required to mediate DC H2-O downregulation in response to LPS. Finally, our studies showed that the mechanism of H2-O downregulation was likely due to direct protein degradation of H2-O as well as downregulation of H2-O mRNA levels. The differential H2-O and H2-M modulation after DC maturation supports the proposed roles of CD8α(-) DCs in initiating CD4-restricted immune responses by optimal MHCII presentation and of CD8α(+) DCs in promoting immune tolerance via presentation of low levels of MHCII-peptide.-
dc.languageeng-
dc.publisherAmerican Association of Immunologists. The Journal's web site is located at http://www.jimmunol.org-
dc.relation.ispartofJournal of Immunology-
dc.rightsThis is an author-produced version of a manuscript accepted for publication in The Journal of Immunology (The JI). The American Association of Immunologists, Inc. (The AAI), publisher of The JI, holds the copyright to this manuscript. This manuscript has not yet been copyedited or subjected to editorial proofreading by The JI; hence, it may differ from the final version published in The JI (online and in print). The AAI (The JI) is not liable for errors or omissions in this author-produced version of the manuscript or in any version derived from it by the National Institutes of Health or any other third party. The final, citable version of record can be found at www.jimmunol.org-
dc.titleTLR agonists downregulate H2-O in CD8a- dendritic cells-
dc.typeArticle-
dc.identifier.emailPorter, GW: porterg@hku.hk-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.4049/jimmunol.1003137-
dc.identifier.pmid21918198-
dc.identifier.pmcidPMC3186832-
dc.identifier.scopuseid_2-s2.0-80054765277-
dc.identifier.hkuros198026-
dc.identifier.volume187-
dc.identifier.issue8-
dc.identifier.spage4151-
dc.identifier.epage4160-
dc.identifier.isiWOS:000295623100027-
dc.publisher.placeUnited States-
dc.identifier.f100013477041-

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