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Updated: Jul 15, 2026

Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
Published on: July 26, 2017
Cell proliferation and survival induced by Toll-like receptors is antagonized by type I IFNs
Uzma A Hasan1, Christophe Caux, Ivan Perrot
1Infections and Cancer Biology Group, International Agency for Research on Cancer (IARC-WHO), 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France. hasan@iarc.fr
Abstract:
TRIF is an adaptor protein associated with the signaling by Toll-like receptor (TLR)3 and TLR4 for the induction of type I IFNs. Here, we demonstrate a mechanism by which TLR signaling controls cell proliferation and survival. We show that TLR3 and TLR4 can induce cell cycle entry via TRIF, which targets the cell cycle inhibitor p27(kip1) for relocalization, phosphorylation by cyclin/cdk complexes, and proteasome degradation. These events are antagonized by type I IFN induced by the TRIF pathway. Furthermore, in human dendritic cells treated with TLR3, TLR4, or TLR5 ligands, we demonstrate that IFN signaling modulates p27(kip1) degradation and apoptosis, identifying an immunoregulatory "switching" function of type I IFNs. These findings reveal a previously uncharacterized function of TLR signaling in cell proliferation and survival.
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