Fever in humans and animals has been shown to generally stimulate the immune system, but its ability to stimulate a specific immune reaction is not clear. Brief exposure to increased temperatures has been shown to affect the immunostimulatory function of dendritic cells. Better understanding of the immune response to fever can contribute to better management of fever in patients.
To determine how the dendritic cell response to hyperthermia affects the adaptive, or specific immune response, researchers investigated whether elevated temperatures (two degrees above normal, 39°C) cause specific gene expression profiles in monocyte-derived dendritic cells. They also explored the possibility of identifying novel hypothermia-related genes. Monocytes from the blood of healthy donors were differentiated into dendritic cells by culturing with granulocyte-macrophage colony-stimulating factor and interleukin-4. Dendritic cells were incubated at 39°C or 37°C (controls) for different time periods and evaluated for gene expression changes using microarray analysis and RT-PCR.
After 3 hours of incubation, microarray analysis identified 43 genes that were up-regulated, and 24 others were down-regulated by the 24-hour time point. These genes belonged to various functional classes including those coding for proteins involved in post-translational modification, protein folding, cell death and survival, and cellular movement. Transcriptional upregulation monitored by RT-PCR confirmed up-regulation of MANF, PLAT and IGFBP6 genes, which code for proteins thought to interact with other immune cells; however, statistical significance was seen only with IGFBP6. IGFBP6 was not upregulated after hyperthermia in other cell lines studied including monocytes. Therefore, upregulation of IGFBP6 is acquired after differentiation into dendritic cells and may be a marker of fever-level temperature.
Using transwells, IGFBP6 protein antibody, and flow cytometry, the chemotactic activity of IGFBP6 was examined in monocytes, T, and B lymphocytes. The addition of IGFBP6 to the cell cultures caused an increase in monocyte and T cell migration. Overall, the results show that human monocyte-derived dendritic cells subjected to hyperthermia have a distinct gene expression profile with a specific up-regulation of IGFBP6. This data helps to unravel information regarding the immune-regulating mechanisms in response to hyperthermia.
Liso A, e. (2017). Human monocyte-derived dendritic cells exposed to hyperthermia show a distinct gene expression profile and selective upregulation of IGFBP6. - PubMed - NCBI . Ncbi.nlm.nih.gov. Retrieved 13 July 2017, from https://www.ncbi.nlm.nih.gov/pubmed/28621669