Dysregulation and impaired anti-bacterial potential of mucosal-associated invariant T cells in autoimmune liver diseases

• DOI: 10.1016/j.intimp.2024.113175
• Publication Date: 2024-09-21T16:04:41Z
• Authors: Wei Wang; Junmei Weng; Haoquan Zhang; Mi Wu; Ting Zhou; Ying Jiang; Xuefen Wu; Cong Ye; Xiufang Weng
• Keywords: Male; Adult; Liver Cirrhosis, Biliary; Ursodeoxycholic Acid; Middle Aged; Mucosal-Associated Invariant T Cells; Anti-Bacterial Agents; Autoimmune Diseases; Hepatitis, Autoimmune; Liver; Escherichia coli; Humans; Cytokines; Female; Cells, Cultured; Aged

Autoimmune liver diseases (AILD) encompass a group of conditions in which the immune system mistakenly attacks the liver tissue. Mucosal-associated invariant T (MAIT) cells are enriched in the liver, where they play crucial roles in antibacterial defense and inflammation regulation. Compared to other autoimmune conditions affecting the synovium of the joints, MAIT cells from AILD exhibited a greater deficiency in ratio, elevated activation markers, increased apoptosis, and higher pro-inflammatory cytokines production. However, the frequency of MAIT cells in AILD was negatively correlated with anti-bacterial indexes, and their impaired responsiveness and weakened anti-bacterial potential were evidenced by reduced expansion ability, lower maximal IFN-γ production, and diminished E. coli-induced cytotoxic mediators release. Similar shifts in MAIT cell ratios and phenotypes were observed in both primary biliary cirrhosis and autoimmune hepatitis, linked to upregulation of bile acid components in the affected tissue. Specifically, ursodeoxycholic acid, a metabolic intermediate and traditional anti-primary biliary cirrhosis drug, inhibited TCR-mediated expansion and downregulated pro-inflammatory cytokines and anti-bacterial-related mediators in MAIT cells. These findings underscore the intricate interplay between hepatic pathology and MAIT cells, and highlight the importance of antibacterial monitoring during ursodeoxycholic acid treatment in AILD.