Serine Supports Epithelial and Immune Cell Function in Colitis.

Overview

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract that are largely driven by immune cell activity, while mucosal healing is critical for remission. Serine is a non-essential amino acid that supports epithelial and immune cell metabolism and proliferation, however, whether these roles impact IBD pathogenesis is not well understood. Here, we show that serine synthesis increases selectively in the epithelial cells of colons from patients with IBD and murine models of colitis. Inhibiting serine synthesis impairs colonic mucosal healing and increases susceptibility to acute injury in mice, effects associated with impaired epithelial cell proliferation. Dietary removal of serine similarly sensitizes mice to acute chemically-induced colitis but ameliorates inflammation in chronic colitis models. The anti-inflammatory effect of exogenous serine depletion in chronic colitis is associated with mitochondrial dysfunction of macrophages, resulting in impaired nucleotide production and proliferation. Collectively, these results suggest that serine plays an important role in both epithelial and immune cell biology in the colon, and that modulating its availability could impact IBD pathogenesis.