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Serine Supports Epithelial and Immune Cell Function in Colitis.

Ji Dong K Bai1, Suchandrima Saha1, Michael C Wood1

  • 1Department of Pathology, Renaissance School of Medicine, Stony Brook University, Stony Brook, New York.

The American Journal of Pathology
|February 28, 2024
PubMed
Summary

Serine synthesis increases in inflammatory bowel disease (IBD) colons. Modulating serine availability impacts gut healing and inflammation by affecting epithelial and immune cell function, offering potential therapeutic strategies for IBD.

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Area of Science:

  • Gastroenterology
  • Immunology
  • Metabolic Research

Background:

  • Inflammatory bowel diseases (IBD) are chronic gastrointestinal disorders driven by immune activity, where mucosal healing is key for remission.
  • Serine, a nonessential amino acid, supports epithelial and immune cell functions, but its role in IBD pathogenesis remains unclear.

Purpose of the Study:

  • To investigate the role of serine metabolism in the pathogenesis of inflammatory bowel diseases (IBD).
  • To determine how serine availability affects mucosal healing and immune responses in the colon during IBD.

Main Methods:

  • Analyzed serine synthesis in colonic epithelial cells from IBD patients and murine colitis models.
  • Utilized mouse models to assess the impact of inhibiting serine synthesis or dietary serine removal on acute and chronic colitis.
  • Examined effects on epithelial cell proliferation, mucosal healing, and macrophage function, including mitochondrial activity and nucleotide production.

Main Results:

  • Serine synthesis was selectively increased in the colons of IBD patients and colitis models.
  • Inhibition of serine synthesis impaired colonic mucosal healing and increased susceptibility to acute injury by reducing epithelial cell proliferation.
  • Dietary serine depletion worsened acute colitis but ameliorated chronic colitis by causing macrophage mitochondrial dysfunction, impairing nucleotide synthesis and proliferation.

Conclusions:

  • Serine plays a critical role in both epithelial and immune cell biology within the colon.
  • Modulating serine availability presents a potential therapeutic avenue for managing inflammatory bowel diseases.
  • Targeting serine metabolism could influence mucosal healing and immune responses in IBD.