Extracellular mRNA Induces Dendritic Cell Activation by Stimulating Tumor Necrosis Factor-α Secretion and Signaling through a Nucleotide Receptor

Houping Ni, John Capodici, Georgetta Cannon, Didier Communi, Jean-Marie Boeynaems, Katalin Karikó, Drew Weissman
<span title="2002-01-30">2002</span> <i title="American Society for Biochemistry &amp; Molecular Biology (ASBMB)"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/mryncoafc5cxdicldzfm4vlsze" style="color: black;">Journal of Biological Chemistry</a> </i> &nbsp;
We previously demonstrated that dendritic cell (DC) pulsing with antigen-encoded mRNA resulted in the loading of both major histocompatibility complex class I and II antigen presentation pathways and the delivery of an activation signal. Coculture of mRNA-pulsed DC with T cells led to the induction of a potent primary immune response. DC, in addition to recognizing foreign antigens through pattern recognition receptors, also must respond to altered self, transformed, or intracellularly infected
more &raquo; ... cells. This occurs through cell surface receptors that recognize products of inflammation and cell death. In this report, we characterize two signaling pathways utilized by extracellular mRNA to activate DC. In addition, a novel ligand, poly(A), is identified that mediates signaling through a receptor that can be inhibited by pertussis toxin and suramin and can be desensitized by ATP and ADP, suggesting a P2Y type nucleotide receptor. The role of this signaling activity in vaccine design and the potential effect of mRNA released by damaged cells in the induction of immune responsiveness is discussed.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1074/jbc.m110729200">doi:10.1074/jbc.m110729200</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/11821398">pmid:11821398</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/yxqt52gmezdhtb7l23dn7datz4">fatcat:yxqt52gmezdhtb7l23dn7datz4</a> </span>
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