Deep in the gut, STAT3 applies Nature's band aid. According to Pickert et al. on page 1465, the signaling protein heals wounded intestines and promotes recovery after colitis.

Eliminating STAT3 from intestinal epithelial cells took no toll on mice until they were treated with the colitis-inducing irritant DSS. While normal mice recuperated after the treatment, those that lacked epithelial STAT3 had problems recovering.

They continued to suffer weight loss, severe tissue damage, and intestinal bleeding after the treatment stopped. Healing required secretion of the cytokine IL-22 from local dendritic cells, which was needed to activate STAT3.

Depending on the disorder, IL-22 and STAT3 can be helpful or harmful. IL-22 exacerbates autoimmunity and STAT3 participates in tumor growth. Other studies suggest that IL-22 protects patients with IBD, perhaps by stimulating the production of antimicrobial peptides.

Here, STAT3 promoted cell growth just as it does when aiding colitis-associated tumors: it prevented the death of epithelial cells around a wound by downregulating death-promoting genes and induced healing with proliferation-inducing genes. Because of its tumor-enhancing tendencies, therapeutic activation of STAT3 in colitis patients must be approached cautiously.

A polymorphism in STAT3 was recently linked to colitis in humans. Perhaps this, or some other mutation, disrupts STAT3 expression, leaving the person vulnerable to intestinal disorders following infection or injury.