4.7 Article

Mast cells and dendritic cells form synapses that facilitate antigen transfer for T cell activation

Journal

JOURNAL OF CELL BIOLOGY
Volume 210, Issue 5, Pages 851-864

Publisher

ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201412074

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Funding

  1. Human Frontiers Science Program Young Investigator Award [RGY0074/2008]
  2. National Institutes of Health [R01GM100114, 5R01AI097202]
  3. New Mexico Spatiotemporal Modeling Center grant [P50GM085273]
  4. Netherlands Organization for Scientific Research (NWO) [836-09-002, 680-47-421]
  5. NWO Medium Sized Investment NWO-ZonMW [91110007]
  6. Grants-in-Aid for Scientific Research [25253071] Funding Source: KAKEN

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Mast cells (MCs) produce soluble mediators such as histamine and prostaglandins that are known to influence dendritic cell (DC) function by stimulating maturation and antigen processing. Whether direct cell-cell interactions are important in modulating MC/DC function is unclear. In this paper, we show that direct contact between MCs and DCs occurs and plays an important role in modulating the immune response. Activation of MCs through FceRI cross-linking triggers the formation of stable cell-cell interactions with immature DCs that are reminiscent of the immunological synapse. Direct cellular contact differentially regulates the secreted cytokine profile, indicating that MC modulation of DC populations is influenced by the nature of their interaction. Synapse formation requires integrin engagement and facilitates the transfer of internalized MC-specific antigen from MCs to DCs. The transferred material is ultimately processed and presented by DCs and can activate T cells. The physiological outcomes of the MC-DC synapse suggest a new role for intercellular crosstalk in defining the immune response.

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