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Cited by 91Immunotherapy and Immune ResponsesT-cell and B-cell ImmunologyImmune Response and Inflammation

Cdc42-mediated MTOC polarization in dendritic cells controls targeted delivery of cytokines at the immune synapse

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Pulecio, Julian, Petrovic, Jelena, Prete, Francesca, Chiaruttini, Giulia, Lennon-Dumenil, Ana-Maria, Desdouets, Chantal, Gasman, Stephane, Burrone, Oscar R. +1 more·2010·Journal of Experimental Medicine
DOI 10.1084/jem.20100007PMC PMC2989776
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Abstract

The immune synapse (IS) forms as dendritic cells (DCs) and T cells interact in lymph nodes during initiation of adaptive immunity. Factors that contribute to the formation and maintenance of IS stability and function have been mostly studied in T cells, whereas little is known about events occurring during synapse formation in DCs. Here, we show that DCs activated by Toll-like receptor (TLR) agonists reorient the microtubule-organizing center (MTOC) toward the interacting T cell during antigen-specific synapse formation through a mechanism that depends on the Rho GTPase Cdc42. IL-12, a pivotal cytokine produced by DCs, is found enriched around the MTOC at early time points after TLR ligation and is dragged to the DC–T cell interface in antigen-specific synapses. Synaptic delivery of IL-12 induces activation of pSTAT4 and IFN-γ neosynthesis in CD8+ naive T cells engaged in antigen-specific conjugates and promotes the survival of antigen-primed T cells. We propose that DC polarization increases the local concentration of proinflammatory mediators at the IS and that this represents a new mechanism by which T cell priming is controlled.

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Crossref · 10.1084/jem.20100007

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  • IL-12 is secreted in a polarized manner from lymphocytes, and this process is dependent on Cdc42.

    “Furthermore, IL-12 is secreted in a polarized manner from lymphocytes; this process is dependent on Cdc42 (52), which also regulates release of TNF to the plasma membrane.”

    From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [52]

    The Results section reports that Cdc42 is required for polarization of intracellular IL-12 at the dendritic-cell–T-cell interface. The Discussion infers preferential secretion there but says secretion at the synapse was not formally demonstrated. The claim incorrectly identifies lymphocytes, rather than dendritic cells, as the IL-12 source. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Cdc42 regulates release of TNF to the plasma membrane.

    “Furthermore, IL-12 is secreted in a polarized manner from lymphocytes; this process is dependent on Cdc42 (52), which also regulates release of TNF to the plasma membrane.”

    From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [52]

    The Discussion (page unavailable) describes TNF secretion as multidirectional in T cells and notes TNF exocytosis in NK cells, but does not link either process to Cdc42. The Results (page unavailable) instead show that Cdc42 regulates polarization of IL-12-containing vesicles in dendritic cells. Searches for TNF release, plasma-membrane delivery, and Cdc42 found no passage establishing the attributed TNF claim. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

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Authors
Pulecio, J., Petrovic, J., Prete, F., Chiaruttini, G., Lennon-Dumenil, A.-M., Desdouets, C., Gasman, S., Burrone, O. R., & Benvenuti, F.
Affiliations
  • International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34149, Trieste, Italy 1
  • International Centre for Genetic Engineering and Biotechnology (IT)
  • Institut National de la Santé et de la Recherche Médicale, U932, Institut Curie, 75005, Paris, France 2
  • Centre National de la Recherche Scientifique (FR)
  • Centre National de la Recherche Scientifique, UPR 3212, Université de Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, 67084 Strasbourg, France 5
Corresponding author
Benvenuti, Federica
ORCID
Venue
Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2010-11-08
Volume
207
Issue
12
Pages
2719-2732
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.20100007
PMC
PMC2989776
OpenAlex
W2121474602
Cited by
91
References
1
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FWCI
3.44
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
Cdc42, microtubule organizing center, dendritic cells, immunological synapse, dendritic cell polarization, IL-12, cytokine delivery, TLR agonists, Rho GTPases, STAT4, interferon-gamma, CD8+ T cell priming, T cell activation, synapse stability
MeSH terms
Animals, Cell Communication, Dendritic Cells, Escherichia coli Infections, Female, Interferon-gamma, Lymphocyte Activation, Mice, Inbred C57BL, T-Lymphocytes, Signal Transduction, Cell Polarity, Interleukin-12, cdc42 GTP-Binding Protein, Microtubule-Organizing Center, Mice, Immunological Synapses

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