Lett, Martin J; Mehta, Hema; Keogh, Adrian; Jaeger, Tina; Jacquet, Maxime; Powell, Kate; Meier, Marie-Anne; Fofana, Isabel; Melhem, Hassan; Vosbeck, Jürg; Cathomas, Gieri; Heigl, Andres; Heim, Markus H; Burri, Emanuel; Mertz, Kirsten D; Niess, Jan Hendrik; Kollmar, Otto; Zech, Christoph J; Ivanek, Robert; Duthaler, Urs; ... (2022). Stimulatory MAIT cell antigens reach the circulation and are efficiently metabolised and presented by human liver cells. Gut, 71(12), pp. 2526-2538. BMJ Publishing Group 10.1136/gutjnl-2021-324478
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OBJECTIVE
Mucosal-associated invariant T (MAIT) cells are the most abundant T cells in human liver. They respond to bacterial metabolites presented by major histocompatibility complex-like molecule MR1. MAIT cells exert regulatory and antimicrobial functions and are implicated in liver fibrogenesis. It is not well understood which liver cells function as antigen (Ag)-presenting cells for MAIT cells, and under which conditions stimulatory Ags reach the circulation.
DESIGN
We used different types of primary human liver cells in Ag-presentation assays to blood-derived and liver-derived MAIT cells. We assessed MAIT cell stimulatory potential of serum from healthy subjects and patients with portal hypertension undergoing transjugular intrahepatic portosystemic shunt stent, and patients with inflammatory bowel disease (IBD).
RESULTS
MAIT cells were dispersed throughout healthy human liver and all tested liver cell types stimulated MAIT cells, hepatocytes being most efficient. MAIT cell activation by liver cells occurred in response to bacterial lysate and pure Ag, and was prevented by non-activating MR1 ligands. Serum derived from peripheral and portal blood, and from patients with IBD stimulated MAIT cells in MR1-dependent manner.
CONCLUSION
Our findings reveal previously unrecognised roles of liver cells in Ag metabolism and activation of MAIT cells, repression of which creates an opportunity to design antifibrotic therapies. The presence of MAIT cell stimulatory Ags in serum rationalises the observed activated MAIT cell phenotype in liver. Increased serum levels of gut-derived MAIT cell stimulatory ligands in patients with impaired intestinal barrier function indicate that intrahepatic Ag-presentation may represent an important step in the development of liver disease.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine 04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery |
UniBE Contributor: |
Keogh, Adrian, Stroka, Deborah |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
0017-5749 |
Publisher: |
BMJ Publishing Group |
Language: |
English |
Submitter: |
Rahel Fuhrer |
Date Deposited: |
08 Jul 2022 08:59 |
Last Modified: |
05 Dec 2022 16:21 |
Publisher DOI: |
10.1136/gutjnl-2021-324478 |
PubMed ID: |
35058274 |
Uncontrolled Keywords: |
antigen presentation fibrosis hepatocyte liver immunology t lymphocytes |
BORIS DOI: |
10.48350/171169 |
URI: |
https://boris.unibe.ch/id/eprint/171169 |
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