Bacteria exposed biliary epithelium and liver B cells activate intrahepatic mait cells in an MR1-dependent manner
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 li...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Elsevier
2015
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| _version_ | 1826282572976488448 |
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| author | Jeffery, H van Wilgenburg, B Kurioka, A Parekh, K Stirling, K Roberts, S Dutton, E Hunter, S Geh, D Braitch, M Rajanayagam, J Iqbal, T Pinkney, T Brown, R Withers, D Adams, D Klenerman, P Oo, Y |
| author_facet | Jeffery, H van Wilgenburg, B Kurioka, A Parekh, K Stirling, K Roberts, S Dutton, E Hunter, S Geh, D Braitch, M Rajanayagam, J Iqbal, T Pinkney, T Brown, R Withers, D Adams, D Klenerman, P Oo, Y |
| author_sort | Jeffery, H |
| collection | OXFORD |
| description | 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.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.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.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. |
| first_indexed | 2024-03-07T00:45:53Z |
| format | Journal article |
| id | oxford-uuid:84a4ddc7-d49d-4e5e-8457-7c40831cda09 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:45:53Z |
| publishDate | 2015 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:84a4ddc7-d49d-4e5e-8457-7c40831cda092022-03-26T21:52:27ZBacteria exposed biliary epithelium and liver B cells activate intrahepatic mait cells in an MR1-dependent mannerJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:84a4ddc7-d49d-4e5e-8457-7c40831cda09EnglishSymplectic Elements at OxfordElsevier2015Jeffery, Hvan Wilgenburg, BKurioka, AParekh, KStirling, KRoberts, SDutton, EHunter, SGeh, DBraitch, MRajanayagam, JIqbal, TPinkney, TBrown, RWithers, DAdams, DKlenerman, POo, YMucosal-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.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.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.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. |
| spellingShingle | Jeffery, H van Wilgenburg, B Kurioka, A Parekh, K Stirling, K Roberts, S Dutton, E Hunter, S Geh, D Braitch, M Rajanayagam, J Iqbal, T Pinkney, T Brown, R Withers, D Adams, D Klenerman, P Oo, Y Bacteria exposed biliary epithelium and liver B cells activate intrahepatic mait cells in an MR1-dependent manner |
| title | Bacteria exposed biliary epithelium and liver B cells activate intrahepatic mait cells in an MR1-dependent manner |
| title_full | Bacteria exposed biliary epithelium and liver B cells activate intrahepatic mait cells in an MR1-dependent manner |
| title_fullStr | Bacteria exposed biliary epithelium and liver B cells activate intrahepatic mait cells in an MR1-dependent manner |
| title_full_unstemmed | Bacteria exposed biliary epithelium and liver B cells activate intrahepatic mait cells in an MR1-dependent manner |
| title_short | Bacteria exposed biliary epithelium and liver B cells activate intrahepatic mait cells in an MR1-dependent manner |
| title_sort | bacteria exposed biliary epithelium and liver b cells activate intrahepatic mait cells in an mr1 dependent manner |
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