Death Begets a New Beginning.

Inflammatory Bowel Disease (IBD) is associated with currently untreatable conditions such as fibrosis and strictures that arise as a consequence of aberrant wound healing. It is of utmost importance that we understand the biology of normal wound healing and discover why IBD is associated instead with abnormal wound healing. Immune cells called macrophages help sense damage and rebuild injured tissues. We have discovered that macrophages promote tissue repair when they sense that cells have died by a specific suicide mechanism called apoptosis. We propose that, if macrophages sense that cells have died by other means such as necroptosis, it is sensed as danger by sentinel macrophages and they respond by producing factors that cause fibrosis. We aim to identify the sensors that macrophages use to identify dead cells and hide the ones that sense danger and promote bad healing, while tricking the macrophages to use their apoptosis sensors that instruct good healing. Our studies have the potential to address a currently unmet need in IBD therapy.