Biliary epithelium and liver B cells exposed to bacteria activate intrahepatic MAIT cells through MR1.
J Hepatol
; 64(5): 1118-1127, 2016 May.
Article
in En
| MEDLINE
| ID: mdl-26743076
ABSTRACT
BACKGROUND & AIMS:
Mucosal-Associated Invariant T (MAIT) cells are innate-like T cells characterised by the invariant TCR-chain, Vα7.2-Jα33, and are restricted by MR1, which presents bacterial vitamin B metabolites. They are important for antibacterial immunity at mucosal sites; however, detailed characteristics of liver-infiltrating MAIT (LI-MAIT) and their role in biliary immune surveillance remain unexplored.METHODS:
The phenotype and intrahepatic localisation of human LI-MAIT cells was examined in diseased and normal livers. MAIT cell activation in response to E. coli-exposed macrophages, biliary epithelial cells (BEC) and liver B cells was assessed with/without anti-MR1.RESULTS:
Intrahepatic MAIT cells predominantly localised to bile ducts in the portal tracts. Consistent with this distribution, they expressed biliary tropic chemokine receptors CCR6, CXCR6, and integrin αEß7. LI-MAIT cells were also present in the hepatic sinusoids and possessed tissue-homing chemokine receptor CXCR3 and integrins LFA-1 and VLA-4, suggesting their recruitment via hepatic sinusoids. LI-MAIT cells were enriched in the parenchyma of acute liver failure livers compared to chronic diseased livers. LI-MAIT cells had an activated, effector memory phenotype, expressed α4ß7 and receptors for IL-12, IL-18, and IL-23. Importantly, in response to E. coli-exposed macrophages, liver B cells and BEC, MAIT cells upregulated IFN-γ and CD40 Ligand and degranulated in an MR1-dependent, cytokine-independent manner. In addition, diseased liver MAIT cells expressed T-bet and RORγt and the cytokines IFN-γ, TNF-α, and IL-17.CONCLUSIONS:
Our findings provide the first evidence of an immune surveillance effector response for MAIT cells towards BEC in human liver; thus they could be manipulated for treatment of biliary disease in the future.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bile Ducts, Intrahepatic
/
B-Lymphocytes
/
Lymphocyte Activation
/
T-Lymphocyte Subsets
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Mucosal-Associated Invariant T Cells
/
Immunity, Innate
/
Liver
Limits:
Humans
Language:
En
Journal:
J Hepatol
Journal subject:
GASTROENTEROLOGIA
Year:
2016
Document type:
Article
Affiliation country:
United kingdom