Melanocyte Stress: Melanocytes in vitiligo patients are abnormal, even when separated from the immune system, suggesting that they have intrinsic defects that contribute to the disease. Some of the characteristics of these abnormal melanocytes include elevated levels of reactive oxygen species (ROS) and activation of the unfolded protein response (UPR). The chemical monobenzone has been shown to worsen vitiligo in patients, and also increases ROS and activates the UPR in melanocytes. This and other similar chemicals may serve as environmental exposures that initiate or worsen vitiligo.
It is likely that these melanocyte stress pathways induce inflammation by generating signals to activate innate immune cells, however the signals and cells that sense those signals are only recently becoming recognized. Previous studies have implicated HSP70, a heat shock protein, and exosomes, secreted cell-derived nanoparticles, as potentially important signals that promote inflammation. We have described these concepts in a recent review article:
|Melanocyte Stress and Innate Immune Activation|
We are exploring these signals and pathways to better understand how vitiligo begins.