To better understand the disease's apparent link to the developing and still immature infant immune system, researchers in this study analyzed the livers of infants diagnosed with biliary atresia. They discovered elevated populations of NK cells in the bile ducts. The NK cells over-expressed genes involved in creating substances that are cytotoxic, or toxic to living cells. This finding led the research team to experiment with a mouse model of biliary atresia.
In the mouse experiments, the scientists used a rotavirus infection to induce biliary atresia in newborn mice. Similar to what was observed in diseased human infant livers, the researchers found that active NK cells were the most abundant cells populating the mouse livers and bile ducts at the time of obstruction. Furthermore, they discovered that NK cells rely on the receptor gene, Nkg2d, to make contact with and attack bile duct surface cells by attaching to the Nk2d protein, which resides on the membranes of bile duct cells. Once that contact is established, NK cells break down the membranes of bile duct surface cells, leading to tissue damage.
When researchers blocked the Nkg2d receptor and depleted the number of NK cells, it prevented damage to bile duct surface tissues, even with the presence of rotavirus infection. The continuity of the mouse pup bile ducts was maintained, bile was able to flow from the liver to the intestines, and the animals grew well into adulthood without liver-related symptoms.
|Contact: Nick Miller|
Cincinnati Children's Hospital Medical Center