According to the Montreal classification, ulcerative colitis (UC) disease scope varies from how much of the colon is affected, with lesser colon involvement called proctitis (E1) and extensive disease called pancolitis (E3). These differing extents impact rates of hospitalization, chance of colectomy, and cancer risk. When the extent of UC is limited (E1 or E2) there is always a sharp demarcation between macroscopically involved and uninvolved areas, although the underlying cause(s) of the clear separation between healthy and unhealthy tissues is unknown. We suspect that this line is determined by antibody-mediated damage to the nervous system that is connected to the colon, because nerves organization in bands around the colon is consistent with the disease pattern. This proposal will investigate this remarkable feature of UC, trying to determine the underlying causes, which may lead to a better understanding of the drivers of disease and progression.