MEDICINE AND HEALTH

The new study provides a target for the treatment of primary biliary cholangitis


Recently, the Journal of Hepatology published the research results of Ma Xiong’s research group of Professor Ma Xiong of the Department of Gastroenterology of Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine online. The study found for the first time that CD103+ TRM cells are the main components of autoantigen-specific CD8+ T cells in the liver of patients with primary biliary cholangitis (PBC), while the nucleotide pool oxidation repair protein NUDT1 is critical for the long-term survival of the pathogenic CD103+ TRM in the liver, which provides a novel specific therapeutic target for PBC.

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The study was published online in the Journal of Hepatology courtesy of respondents

Ma Xiong said that PBC is the most common autoimmune liver disease, formerly known as “primary biliary cirrhosis”. The base of PBC patients in China is very large, and the prevalence of women over 40 years old is about one in a thousand, of which 30% to 40% of patients respond poorly to standardized treatment or cannot tolerate the drug. Moreover, immune-targeted therapies are still lacking.

Positive antimitochondrial antibody (AMA) is the most typical serum immunological feature of PBC, and the autoantigen recognized by AMA is mainly the pyruvate dehydrogenase E2 subunit (PDC-E2) in the mitochondria, and PDC-E2-specific CD8+ T cells play a key role in bile duct damage of PBC. Studies have shown that a variety of autoimmune diseases may be driven by tissue-resident memory T (TRM) cells, a recently discovered subset of new memory T cells that reside in specific tissues for a long time and are not involved in recycling. It is based on this characteristic that some scholars have proposed that it may cause problems with autoimmune diseases.

The team found that CD103+ TRM cells in PBC livers were significantly expanded and overactivated, and they were the main components of PDC-E2-specific autoreactive CD8+ T cells.

“Targeting NUDT1 to inhibit the number and function of CD103+ TRM cells in the liver may help alleviate immune bile duct damage in patients with PBC.” Ma Xiong said, “This therapy highly selectively inhibits autoantigen-specific CD8+ T cells, which can achieve the purpose of immunosuppressive therapy and greatly reduce side effects such as off-target toxicity to PBC patients, and has considerable clinical translational value.” (Source: China Science Daily, Zhang Shuanghu, Huang Xin)

Related paper information:https://doi.org/10.1016/j.jhep.2022.06.014



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