October 6, 2022 -- Researchers have discovered a link between the protein apoptosis inhibitor five (API5) and Crohn's disease. They found API5 protects most people with the mutation that makes gut lining cells more vulnerable to damage, like in Crohn's disease, until a second trigger -- such as norovirus infection -- takes hold (Nature, October 5, 2022).
The New York University Langone Health researchers genetically modified mice to have the mutation linked to Crohn's disease. Mice injected with API5 survived whereas half the untreated group died. In human tissue, the researchers discovered those with Crohn's disease had between fivefold and tenfold fewer API5-producing T cells in their gut tissue than those without the illness.
The scientists also created organoids from gut-lining cells positive for the Crohn's disease mutation. When API5 was injected into these "mini guts," the gut-lining cells were protected. It seems when norovirus infects those with a weakened ability to produce API5, it tips the scales toward autoimmune disease, according to the authors.
While the researchers worked with human tissue, it's unclear whether API5 can be injected safely into humans. However, most Crohn's disease therapies work by suppressing the immune system and not only put patients at high risk for infection but also become less effective after a few years. A treatment involving API5 could be a better solution and the researchers plan to explore the long-term effects of the injections.
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