Human monocyte-derived dendritic cells exposed to hyperthermia show a distinct gene expression profile and selective upregulation of IGFBP6

Arcangelo Liso, Stefano Castellani, Francesca Massenzio, Rosa Trotta, Alessandra Pucciarini, Barbara Bigerna, Pasquale De Luca, Pietro Zoppoli, Filippo Castiglione, Maria Concetta Palumbo, Fabrizio Stracci, Matteo Landriscina, Giorgina Specchia, Leon A Bach, Massimo Conese, Brunangelo Falini

Research output: Contribution to journalArticlepeer-review

Abstract

Fever plays a role in activating innate immunity while its relevance in activating adaptive immunity is less clear. Even brief exposure to elevated temperatures significantly impacts on the immunostimulatory capacity of dendritic cells (DCs), but the consequences on immune response remain unclear. To address this issue, we analyzed the gene expression profiles of normal human monocyte-derived DCs from nine healthy adults subjected either to fever-like thermal conditions (39°C) or to normal temperature (37°C) for 180 minutes. Exposure of DCs to 39°C caused upregulation of 43 genes and downregulation of 24 genes. Functionally, the up/downregulated genes are involved in post-translational modification, protein folding, cell death and survival, and cellular movement. Notably, when compared to monocytes, DCs differentially upregulated transcription of the secreted protein IGFBP-6, not previously known to be specifically linked to hyperthermia. Exposure of DCs to 39°C induced apoptosis/necrosis and resulted in accumulation of IGFBP-6 in the conditioned medium at 48 h. IGFBP-6 may have a functional role in the hyperthermic response as it induced chemotaxis of monocytes and T lymphocytes, but not of B lymphocytes. Thus, temperature regulates complex biological DC functions that most likely contribute to their ability to induce an efficient adaptive immune response.

Original languageEnglish
Pages (from-to)60826-60840
Number of pages15
JournalOncotarget
Volume8
Issue number37
DOIs
Publication statusPublished - Sep 22 2017

Keywords

  • Journal Article

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