Bile from Patients with Primary Sclerosing Cholangitis Contains Mucosal-Associated Invariant T Cell Antigens

Am J Pathol. 2022 Jan 18:S0002-9440(22)00008-6. doi: 10.1016/j.ajpath.2021.12.008. Online ahead of print.ABSTRACTPrimary sclerosing cholangitis (PSC) is associated with altered microbiota of the gut and bile. Mucosal-associated invariant T (MAIT) cells are enriched in human liver and uniquely recognizes microbial-derived metabolites. We aimed to determine if bile from patients with PSC contains antigens activating MAIT cells. Bile was collected at the time of liver transplantation from patients with PSC (n=28). The bile samples were either directly incubated with peripheral blood mononuclear cells (PBMCs) from healthy donors, or with antigen presenting cells followed by co-culture with PBMCs. MAIT cell activation was assessed by flow cytometry. To determine if the activation was MR1 restricted, an anti-MR1 antibody was used. Biliary microbiota profiles were generated using 16S rRNA amplicon sequencing and the abundance of the bacterial gene ribD was predicted. Eight of 28 bile samples could activate MAIT cells. This activation was partly MR1-dependent in five of eight bile samples. Microbial DNA was detected in 15 out of 28 bile samples, including the five bile samples leading to MR1 dependent activation. A higher abundance of the ribD gene expression in the group of bile samples that could activate MAIT cells was predicted based on the 16s sequencing. In co-culture experiments cholangiocytes could take up and present biliary antigens to MAIT cells. These findings suggest a p...
Source: The American Journal of Pathology - Category: Pathology Authors: Source Type: research