TCR and Inflammatory Signals Tune Human MAIT Cells to Exert Specific Tissue Repair and Effector Functions
Summary: MAIT cells are an unconventional T cell population that can be activated through both TCR-dependent and TCR-independent mechanisms. Here, we examined the impact of combinations of TCR-dependent and TCR-independent signals in human CD8+ MAIT cells. TCR-independent activation of these MAIT ce...
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| Format: | Article |
| Language: | English |
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Elsevier
2019-09-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719310988 |
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doaj-f78e3319ea4b4781a9075ab9de1e2008 |
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Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Tianqi Leng Hossain Delowar Akther Carl-Philipp Hackstein Kate Powell Thomas King Matthias Friedrich Zoe Christoforidou Sarah McCuaig Mastura Neyazi Carolina V. Arancibia-Cárcamo Joachim Hagel Fiona Powrie Raphael Sanches Peres Val Millar Daniel Ebner Rajesh Lamichhane James Ussher Timothy S.C. Hinks Emanuele Marchi Chris Willberg Paul Klenerman |
| spellingShingle |
Tianqi Leng Hossain Delowar Akther Carl-Philipp Hackstein Kate Powell Thomas King Matthias Friedrich Zoe Christoforidou Sarah McCuaig Mastura Neyazi Carolina V. Arancibia-Cárcamo Joachim Hagel Fiona Powrie Raphael Sanches Peres Val Millar Daniel Ebner Rajesh Lamichhane James Ussher Timothy S.C. Hinks Emanuele Marchi Chris Willberg Paul Klenerman TCR and Inflammatory Signals Tune Human MAIT Cells to Exert Specific Tissue Repair and Effector Functions Cell Reports |
| author_facet |
Tianqi Leng Hossain Delowar Akther Carl-Philipp Hackstein Kate Powell Thomas King Matthias Friedrich Zoe Christoforidou Sarah McCuaig Mastura Neyazi Carolina V. Arancibia-Cárcamo Joachim Hagel Fiona Powrie Raphael Sanches Peres Val Millar Daniel Ebner Rajesh Lamichhane James Ussher Timothy S.C. Hinks Emanuele Marchi Chris Willberg Paul Klenerman |
| author_sort |
Tianqi Leng |
| title |
TCR and Inflammatory Signals Tune Human MAIT Cells to Exert Specific Tissue Repair and Effector Functions |
| title_short |
TCR and Inflammatory Signals Tune Human MAIT Cells to Exert Specific Tissue Repair and Effector Functions |
| title_full |
TCR and Inflammatory Signals Tune Human MAIT Cells to Exert Specific Tissue Repair and Effector Functions |
| title_fullStr |
TCR and Inflammatory Signals Tune Human MAIT Cells to Exert Specific Tissue Repair and Effector Functions |
| title_full_unstemmed |
TCR and Inflammatory Signals Tune Human MAIT Cells to Exert Specific Tissue Repair and Effector Functions |
| title_sort |
tcr and inflammatory signals tune human mait cells to exert specific tissue repair and effector functions |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2019-09-01 |
| description |
Summary: MAIT cells are an unconventional T cell population that can be activated through both TCR-dependent and TCR-independent mechanisms. Here, we examined the impact of combinations of TCR-dependent and TCR-independent signals in human CD8+ MAIT cells. TCR-independent activation of these MAIT cells from blood and gut was maximized by extending the panel of cytokines to include TNF-superfamily member TL1A. RNA-seq experiments revealed that TCR-dependent and TCR-independent signals drive MAIT cells to exert overlapping and specific effector functions, affecting both host defense and tissue homeostasis. Although TCR triggering alone is insufficient to drive sustained activation, TCR-triggered MAIT cells showed specific enrichment of tissue-repair functions at the gene and protein levels and in in vitro assays. Altogether, these data indicate the blend of TCR-dependent and TCR-independent signaling to CD8+ MAIT cells may play a role in controlling the balance between healthy and pathological processes of tissue inflammation and repair. : Leng et al. explore the consequences of activation of human MAIT cells via their TCR and/or cytokines, including the gut-associated TNF-superfamily member TL1A. TCR triggering reveals a transcriptional program linked to tissue-repair functions seen in vivo, consistent with a homeostatic role for these cells in epithelia. Keywords: MAIT cells, effector functions, TCR signaling, cytokines, tissue repair |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124719310988 |
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doaj-f78e3319ea4b4781a9075ab9de1e20082020-11-24T23:57:12ZengElsevierCell Reports2211-12472019-09-01281230773091.e5TCR and Inflammatory Signals Tune Human MAIT Cells to Exert Specific Tissue Repair and Effector FunctionsTianqi Leng0Hossain Delowar Akther1Carl-Philipp Hackstein2Kate Powell3Thomas King4Matthias Friedrich5Zoe Christoforidou6Sarah McCuaig7Mastura Neyazi8Carolina V. Arancibia-Cárcamo9Joachim Hagel10Fiona Powrie11Raphael Sanches Peres12Val Millar13Daniel Ebner14Rajesh Lamichhane15James Ussher16Timothy S.C. Hinks17Emanuele Marchi18Chris Willberg19Paul Klenerman20Peter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, UKPeter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, UK; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford OX3 9DU, UKPeter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, UK; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford OX3 9DU, UKPeter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, UK; Department of Microbiology and Immunology, University of Otago, Otago, New ZealandPeter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, UKThe Kennedy Institute of Rheumatology, Roosevelt Dr., Oxford OX3 7FY, UKTranslational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford OX3 9DU, UKThe Kennedy Institute of Rheumatology, Roosevelt Dr., Oxford OX3 7FY, UKThe Kennedy Institute of Rheumatology, Roosevelt Dr., Oxford OX3 7FY, UKTranslational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford OX3 9DU, UKPeter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, UKThe Kennedy Institute of Rheumatology, Roosevelt Dr., Oxford OX3 7FY, UKThe Kennedy Institute of Rheumatology, Roosevelt Dr., Oxford OX3 7FY, UKTarget Discovery Institute, Roosevelt Dr., Oxford OX3 7FZ, UKTarget Discovery Institute, Roosevelt Dr., Oxford OX3 7FZ, UKDepartment of Microbiology and Immunology, University of Otago, Otago, New ZealandDepartment of Microbiology and Immunology, University of Otago, Otago, New ZealandNIHR Biomedical Research Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK; Respiratory Medicine Unit, Nuffield Department of Medicine Experimental Medicine, University of Oxford, Oxford OX3 9DU, UK; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, AustraliaPeter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, UKPeter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, UKPeter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, UK; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford OX3 9DU, UK; NIHR Biomedical Research Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK; Corresponding authorSummary: MAIT cells are an unconventional T cell population that can be activated through both TCR-dependent and TCR-independent mechanisms. Here, we examined the impact of combinations of TCR-dependent and TCR-independent signals in human CD8+ MAIT cells. TCR-independent activation of these MAIT cells from blood and gut was maximized by extending the panel of cytokines to include TNF-superfamily member TL1A. RNA-seq experiments revealed that TCR-dependent and TCR-independent signals drive MAIT cells to exert overlapping and specific effector functions, affecting both host defense and tissue homeostasis. Although TCR triggering alone is insufficient to drive sustained activation, TCR-triggered MAIT cells showed specific enrichment of tissue-repair functions at the gene and protein levels and in in vitro assays. Altogether, these data indicate the blend of TCR-dependent and TCR-independent signaling to CD8+ MAIT cells may play a role in controlling the balance between healthy and pathological processes of tissue inflammation and repair. : Leng et al. explore the consequences of activation of human MAIT cells via their TCR and/or cytokines, including the gut-associated TNF-superfamily member TL1A. TCR triggering reveals a transcriptional program linked to tissue-repair functions seen in vivo, consistent with a homeostatic role for these cells in epithelia. Keywords: MAIT cells, effector functions, TCR signaling, cytokines, tissue repairhttp://www.sciencedirect.com/science/article/pii/S2211124719310988 |