Research Papers: Immunology:

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 and Brunangelo Falini

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Oncotarget. 2017; 8:60826-60840. https://doi.org/10.18632/oncotarget.18338

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Arcangelo Liso1, Stefano Castellani1, Francesca Massenzio1, Rosa Trotta1, Alessandra Pucciarini2, Barbara Bigerna2, Pasquale De Luca3, Pietro Zoppoli4, Filippo Castiglione5, Maria Concetta Palumbo5, Fabrizio Stracci6, Matteo Landriscina1,7, Giorgina Specchia8, Leon A. Bach9,10, Massimo Conese1 and Brunangelo Falini2

1 Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy

2 Institute of Haematology, University of Perugia, Perugia, Italy

3 Stazione Zoologica A. Dohrn, Naples, Italy

4 Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi Magna Graecia, Catanzaro, Italy

5 Institute for Applied Computing, National Research Council of Italy, Rome, Italy

6 Department of Experimental Medicine, Section of Public Health, University of Perugia, Perugia, Italy

7 Laboratory of Preclinical and Translational Research, IRCCS, Referral Cancer Center of Basilicata, Rionero in Vulture, Italy

8 Institute of Hematology, University of Bari, Bari, Italy

9 Department of Medicine, Alfred Hospital, Monash University, Melbourne, Australia

10 Department of Endocrinology and Diabetes, Alfred Hospital, Melbourne, Australia

Correspondence to:

Arcangelo Liso, email:

Massimo Conese, email:

Keywords: apoptosis, B cells, chemotaxis, dendritic cells, hyperthermia, Immunology and Microbiology Section, Immune response, Immunity

Received: April 16, 2017 Accepted: May 12, 2017 Published: June 01, 2017


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.

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