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COMPASS pathway enables regulatory T cells to prevent devastating autoimmune responses to gut bacteria

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COMPASS pathway enables regulatory T cells to prevent devastating autoimmune responses to gut bacteria

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Trillions of bacteria live in the human gut without triggering an immune response. Scientists at St. Jude Children's Research Hospital have now discovered a gene-regulatory pathway that helps maintain this delicate balance. In a study published in Science Advances, they show that regulatory T cells, a type of immune cell, co-opt a well-known general gene expression pathway called COMPASS to suppress inappropriate immune responses and prevent lethal inflammation and autoimmunity.

Within the body, immune cells distinguish between self and nonself, eliminating that which they consider nonself, such as viruses and bacteria. In the gut, this is complicated by the presence of the intestinal microbiota, a community of beneficial bacteria that live there. Regulatory T cells stop other immune cells from inappropriately reacting to these bacteria, though the genetic factors that govern the process were poorly understood.

To identify those factors, the St. Jude scientists used a CRISPR screen, uncovering that the gene Wdr82, a key component of the gene activation pathway COMPASS, plays an essential role in enabling regulatory T cells to maintain intestinal immune tolerance.

, St. Jude Department of Immunology.



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