Dendritic cell function at low physiological temperature

DC are differentially regulated by low temperature and this can affect DC in inflammation, migration, and T cell activation. Compared with the stable core temperature, the skin temperature is lower and varies depending on ambient temperature and convection conditions. The function of DCs, which are plentiful in the skin at lower physiological temperatures, has not been reported. We show that DC performed some functions normally at 28°C, including phagocytosis and macropinocytosis. TLR-4 signaling via MAPK pathways was delayed at 28°C but reached normal levels, which may explain the observed slower kinetics of stimulated macropinocytosis and TNF production. TLR-4-induced NO production was compromised severely at 28°C. Collagen degradation and migration through matrigel-coated transwell inserts were decreased, but no effect on podosome number or DC migration through noncoated transwell filters was seen. Lowering the temperature differentially regulated functions associated with the role of DCs in adaptive immunity. LPS-induced up-regulation of CD86 was normal; however, CD40 up-regulation was suppressed after TLR-4 stimulation at 28°C. Nonactivated DC processed and presented antigen on MHC class II equally well at 28°C and 37°C. However, DCs that were loaded with antigens and stimulated with TLR ligand at 28°C were poor at activating T cells at 37°C compared with DCs that were activated and loaded with antigen at 37°C.