Mast cells and dendritic cells form synapses that facilitate antigen transfer for T cell activation.
Bottom Line: 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.
Affiliation: Department of Pathology, The University of New Mexico School of Medicine, Albuquerque, NM 87131.Show MeSH
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Mentions: As immune modulators, both MCs and DCs are capable of secreting a wide variety of cytokines to stimulate or repress immune responses. To determine whether direct cell–cell interactions might influence cellular responses, cytokine secretion was measured using ELISA. MCs and imDCs were co-incubated to allow for either direct or indirect (with transwell separation) interactions. To activate MCs, FcεRI signaling was initiated by the addition of the multivalent antigen, DNP-BSA, which cross-links the DNP-specific IgE bound to the receptor. Supernatants from 2- and 12-h co-cultures were collected for ELISAs. Of the cytokines tested (IL1ra, MIP1α, MCP-1, IL-4, IL-6, IL-10, IL-12, TNF, and TIMP-1), IL-1ra, MIP1α, and MCP-1 showed consistent changes during the co-incubation (Fig. 2). We found several different modes by which direct MC–DC contact can modulate cytokine responses. IL-1ra secretion by DCs is significantly up-regulated only when DCs were allowed to be in direct contact with actMCs (Fig. 2, left, compare DC with DC+actMC). On the other hand, MCP-1 secreted by actMCs was down-regulated when MCs and DCs were not in contact, but direct MC–DC interaction prevented this down-regulation (Fig. 2, top right, compare DC+actMC with DC+actMC_TW). MIPα secretion by actMCs was down-regulated in the presence of DCs, but direct MC–DC interaction delayed this down-regulation (Fig. 2, center, compare 2 h and 12 h DC+actMC). We note that TNF consistently increased with activation of MCs as expected (Fig. 2, bottom, right graph). These data indicate that cytokine production by MCs and DCs is differentially regulated depending on whether direct cellular interaction occurs. We postulate that the formation of cell–cell contacts alters cell signaling, likely through activation of adhesion molecules, and leads to changes in the quality and the timing of the cytokine response.
Affiliation: Department of Pathology, The University of New Mexico School of Medicine, Albuquerque, NM 87131.