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

Am J Pathol. 2022 Apr;192(4):629-641. doi: 10.1016/j.ajpath.2021.12.008. Epub 2022 Jan 19.

Abstract

Primary sclerosing cholangitis (PSC) is associated with altered microbiota of the gut and bile. Mucosal-associated invariant T (MAIT) cells, enriched in human liver, uniquely recognize microbial-derived metabolites. This study aimed to determine whether 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 from healthy donors or with antigen-presenting cells followed by co-culture with peripheral blood mononuclear cells. MAIT cell activation was assessed by flow cytometry. An anti-MR1 antibody was used to determine whether the activation was major histocompatibility complex class I-related protein (MR1) restricted. 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 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 on the basis of the 16S sequencing. In co-culture experiments, cholangiocytes could take up and present biliary antigens to MAIT cells. These findings suggest a pathophysiological pathway in PSC connecting the immune system and the microbiome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens
  • Bile / metabolism
  • Cholangitis, Sclerosing*
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Mucosal-Associated Invariant T Cells*
  • RNA, Ribosomal, 16S

Substances

  • Antigens
  • Histocompatibility Antigens Class I
  • RNA, Ribosomal, 16S