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Scientists at St. Jude Children's Research Hospital have identified a gene-regulatory pathway — called COMPASS — that helps immune cells keep gut bacteria from triggering dangerous inflammation. When a key gene in this pathway was disabled in mice, severe intestinal inflammation and autoimmunity followed. The findings could reshape how researchers approach inflammatory bowel disease and other autoimmune conditions.
Your gut is home to trillions of bacteria, and a specialized group of immune cells — regulatory T cells — are what keep your body from attacking them. Now, researchers at St. Jude Children's Research Hospital have pinpointed exactly how those cells do their job, identifying a gene-regulatory pathway called COMPASS as a critical gatekeeper of intestinal immune tolerance. The findings were published in Science Advances.
Using a CRISPR screen, the team zeroed in on a gene called Wdr82, a key component of the COMPASS pathway. When they deleted Wdr82 in mouse T cells, the animals developed severe — and ultimately lethal — intestinal inflammation and autoimmunity. Restoring functional regulatory T cells reversed the damage. Antibiotic treatment, which cleared most gut bacteria, also halted the inflammatory cascade, confirming that the immune system was reacting to the microbiome itself.
Key Takeaways:
Why it matters: This research challenges a long-held assumption in immunology and could help explain cases of autoimmunity that have stumped scientists — pointing toward novel, targeted therapies for conditions that currently have no cure.
