Uric acid speaks of danger

The immune system reacts when it encounters antigens associated with a potential threat, such as infection, and it is microbial components that stimulate dendritic cells to mature so that they can present foreign antigens and subsequently stimulate T lymphocytes. Dying mammalian cells also release biochemical danger signals, but the identity of these signals has been unclear. In the September 7 Nature, Yan Shi and colleagues from University of Massachusetts Medical School show that uric acid is a principal endogenous cellular danger signal that alerts the immune system to dying cells (Nature, DOI:10.1038/nature01991, September 7, 2003).

Shi et al. used mass spectrometry and isolated uric acid as the active molecule in fractionated cytosol from irradiated BALB/c 3T3 cells. When uric acid was coinjected with antigen in vivo, it significantly enhanced the generation of responses from CD81 T cells. In addition, the authors showed that eliminating uric acid in vivo inhibited the ...