Immunoregulatory effects of HO-1: how does it work?

The heme-catabolizing enzyme heme oxygenase-1 (HO-1; encoded by the Hmox1 gene) inhibits the pathogenesis of several immune-mediated inflammatory diseases. This unusually broad salutary effect is thought to rely on the immunoregulatory actions of HO-1, exerted on innate and adaptive immune cells. According to this notion, HO-1 'dampens' innate and adaptive immune responses, limiting immune-mediated tissue injury and thus suppressing the pathogenesis of immune-mediated inflammatory diseases. We will argue that the salutary effects of HO-1 are also exerted via its cytoprotective action, which sustains tissue function and prevents unfettered immune activation by endogenous proinflammatory ligands released from injured cells.