Projects per year
Abstract
BACKGROUND: 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 αEβ7. 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 α4β7 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 up-regulated 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 biliary epithelial cells in human liver; thus they could be manipulated for treatment of biliary disease in the future.
Original language | English |
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Pages (from-to) | 1118–1127 |
Journal | Journal of Hepatology |
Volume | 64 |
Issue number | 5 |
Early online date | 29 Dec 2015 |
DOIs | |
Publication status | Published - May 2016 |
Keywords
- MAIT
- Bile ducts
- MR1
- Liver
- Human liver
- Mucosal-associated invariant T cells
- Biliary epithelium
- E. coli
- Immune response
- Biliary firewall
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Dive into the research topics of 'Biliary epithelium and liver B cells exposed to bacteria activate intrahepatic MAIT cells through MR1'. Together they form a unique fingerprint.Projects
- 2 Finished
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Intrahepatic Signals Involve in the Recruitment and Differentiation of IL-17 Secreting T Cells and Regulatory T Cells in Chronic Hepatitis - Fellowship
Oo, Y. (Principal Investigator)
4/01/12 → 5/01/18
Project: Research Councils
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MRC Centre For Immune Regulation (Linked to DCDF.RRAK10540) (Linked to 14810 & 14835)
Jenkinson, E. (Principal Investigator)
3/08/09 → 30/09/17
Project: Research Councils