HOXA11os, an IBD associated lncRNA that maintains tissue homeostasis and restrains inflammation.

The intestinal immune system must maintain a delicate balance between harmless bacteria in the gut and immunity against dangerous pathogens. Dysregulation of this balance can lead to Inflammatory Bowel Diseases (IBD) such as ulcerative colitis (UC) and Crohn’s disease. Many treatments for IBD focus on blocking inflammation and fail to repair damaged tissue and restore the integrity of the tissue. We have identified a long non-coding RNA that is only expressed in the colon. When this RNA is present the tissue is healthy and functional. In patients with ulcerative colitis however, the levels of this lncRNA decrease. To model this state, we generated mice lacking this lncRNA and like patients with UC, these mice develope colitis. The lncRNA localizes to the mitochondria in cells of the healthy colon. When the lncRNA is lost, the mitochondria in the cells in the colon are damaged, produce reactive oxygen species and damage colonic tissue. These findings provide new insights into how a lncRNA can help mitochondria work well to maintain homeostasis in the gut. These studies suggest new opportunities to restore tissue health by controlling the levels of this lncRNA.