| The immune system plays an essential role in protecting the host against infections and to accomplish this task has evolved mechanisms to recognize microbes and destroy them. In addition, it monitors the health of cells and responds to ones that are under stress, in the process of dying or death, even if this occurs under sterile conditions. In the liver, this process is often initiated when damage hepatocytes that are undergoing cell death expose intracellular molecules that can be recognized by cells of the innate immune system. As a consequence of this recognition, dendritic cells are activated in ways that help to promote T-cell responses to antigens associated with the dying cells. Additionally, resident macrophages or Kupffer cells are stimulated to produce the cytokine interleukin-1 that may then act on hepatocytes and non-parenchymal cells in the liver in ways that drive a robust inflammatory response. In addition to dead cells, a number of other sterile particles and altered physiological states can similarly stimulate an inflammatory response and do so through common pathways involving the inflammasome and interleukin-1. These pathways are evolving as key players in a number of acute and chronic liver diseases. In this symposium, I will discuss new insights into specific triggers of sterile inflammation, the role of inflammasomes, and downstream signals that contribute to liver damage and fibrosis, as well as the implications for the development of anti-fibrotic strategies. |
