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Benitez-Ribas, DanielAuthor
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Activation of human plasmacytoid dendritic cells by TLR9 impairs FcγRII-mediated uptake of immune complexes and presentation by MHC class II

Publicated to:Journal Of Immunology. 181 (8): 5219-5224 - 2008-10-15 181(8), DOI: 10.4049/jimmunol.181.8.5219

Authors: Benitez-Ribas, Daniel; Tacken, Paul; Punt, Cornelis J A; de Vries, I Jolanda M; Figdor, Carl G

Affiliations

Radboud Univ Nijmegen, Med Ctr, Dept Med Oncol, NL-6525 ED Nijmegen, Netherlands - Author
Radboud Univ Nijmegen, Med Ctr, Dept Pediat Oncol, NL-6525 ED Nijmegen, Netherlands - Author
Radboud Univ Nijmegen, Med Ctr, Dept Tumor Immunol, NL-6525 ED Nijmegen, Netherlands - Author

Abstract

Human plasmacytoid dendritic cells (pDCS)(2) exploit Ag uptake receptors like CD32a for internalization of exogenous Ags. Activation of pDC by TLR9 ligand CpG-C induces strong maturation. Surprisingly, we observed that CpG-C-stimulated pDCs showed impaired Ag-specific T cell proliferation whereas the induction of allogeneic T cell proliferation was not-affected. We demonstrated that signals from TLR9 caused a rapid down-regulation of the capacity of pDC to take-up Ab-Ag complexes without altering their CD32a expression, thus explaining the reduced Ag presentation. The recent contrasting biological responses that were observed upon TLR9 ligation in pDCs prompted us to study the effect of several TLR9 ligands. We observed that type I IFN-inducer CpG-A, localizing in the early endosomal compartment, did not affect CD32a function, whereas CpGs localizing in the late endosomes and inducing pDC maturation clearly inhibited CD32a-mediated Ag uptake and presentation. We conclude that TLR9 ligands not only determine the type of response, i.e., type I IFN production (innate immunity) or maturation (adaptive immunity), but also directly affect Ag presentation capacity of pDCs. We hypothesize that pDC, once activated via TLR9-ligands reaching the late endosomes, can only present initially sampled Ags and thus are protected from uptake and processing of additional potential self-Ags.

Keywords
Adaptive immunityAlpha interferonAntigenAntigen antibody complexAntigen captureAntigen presentationAntigen-antibody complexAntigensArticleB7 antigenCd32 antigenCd4(+) t-cellsCd86 antigenCell maturationCell proliferationCpCpg a 2336Cpg islandCpg oligonucleotideCpg-a 2336Cpg-oligonucleotideCytologyDc-signDendritic cellDendritic cellsDown regulationDrug effectDrug potentiationEndosomeEndosomesExpressionFc receptorFc receptor iiaGene expression regulationHistocompatibility antigens class iiHla antigen class 2HumanHumansIfn-alpha productionImmunity, naturalImmunologyInnate immunityInterferonInterferon productionInterferon type iInterferon-producing-cellsLigandLigandsMajor histocompatibility antigen class 2Melanoma patientsMetabolismOligodeoxyribonucleotideOligodeoxyribonucleotidesPhysiologyPlasma cellPlasma cellsPriority journalProtein expressionReceptorReceptors, iggResponsesT lymphocyteT-lymphocytesTlr9 protein, humanToll like receptor 9Toll-like receptor 9

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Journal Of Immunology due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2008, it was in position 16/121, thus managing to position itself as a Q1 (Primer Cuartil), in the category Immunology.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 2.75, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Apr 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-04-25, the following number of citations:

  • WoS: 23
  • Scopus: 25
  • OpenCitations: 25
Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-04-25:

  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 42 (PlumX).
Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Netherlands.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Benítez Ribas, Daniel) .