Seoul St. Mary's Hospital, identification of the intestinal-liver IgA immune axis in alcoholic liver disease

Seoul St. Mary’s Hospital “IgA and liver immune cells amplify inflammatory response → liver cell damage”

(Seoul = Yonhap News) Reporter Go Yoo-seon = Research has shown that immunoglobulin A (IgA) antibodies, which protect the intestines, move to the liver and increase inflammation when drinking excessively.

Seoul St. Mary's Hospital of the Catholic University of Korea announced on the 28th that Professor Seong Pil-soo's research team in the Department of Gastroenterology has identified the 'intestinal-liver IgA immune axis', where increased IgA in alcohol-related liver disease causes a strong inflammatory response in the liver and liver cell damage.

IgA is mainly a 'defensive antibody' that blocks bacteria and viruses in the mucous membranes that come in contact with the external environment, such as the intestines and respiratory tract. In particular, in the intestines, it plays an important role in preventing numerous intestinal microorganisms from penetrating into our bodies.

High blood IgA levels have been observed in patients with alcohol-related liver disease, but the reason for this or whether IgA is involved in liver damage has not been clearly identified.

The research team analyzed the patient's blood and liver tissue and looked at the relationship between IgA and liver damage by combining animal models, spatial transcriptome analysis, and human immune cell experiments. As a result, it was confirmed that the higher the level of IgA in the blood, the more IgA accumulated in liver tissue, and the binding of IgA to liver monocytes and macrophages.

This means that if drinking causes changes in the intestinal barrier and IgA produced in the intestines moves to the liver, the inflammatory response of liver macrophages can be activated, leading to liver damage.

In animal models administered alcohol, increased blood IgA, IgA binding to liver macrophages, expression of interleukin-1 beta (IL-1β), which is involved in inflammatory responses, and liver damage were observed.

Conversely, when a drug that regulates immune cell migration (FTY720) was administered, the number of IgA-bound liver macrophages decreased along with blood IgA, and liver damage also decreased.

The researchers explained that, unlike previous studies on the 'intestinal-liver axis' that focused on intestinal microorganisms, this study is meaningful in that it presents the perspective that immune antibodies produced in the intestines can control liver inflammation.

Professor Seong Pil-soo, the corresponding author, emphasized, "Alcohol-related liver disease is a globally important disease, but treatments that directly suppress the disease are still limited. In the future, it is important to more precisely identify the process by which IgA meets specific immune cells in the liver and amplifies inflammation, and find a treatment strategy that can control only the pathological gut-liver IgA immune axis while maintaining immune function."

This study was published in Gut, an international academic journal in the field of digestive and liver diseases.