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TCR and Inflammatory Signals Tune Human MAIT Cells to Exert Specific Tissue Repair and Effector Functions

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 fro...

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Autores principales: Leng, Tianqi, Akther, Hossain Delowar, Hackstein, Carl-Philipp, Powell, Kate, King, Thomas, Friedrich, Matthias, Christoforidou, Zoe, McCuaig, Sarah, Neyazi, Mastura, Arancibia-Cárcamo, Carolina V., Hagel, Joachim, Powrie, Fiona, Peres, Raphael Sanches, Millar, Val, Ebner, Daniel, Lamichhane, Rajesh, Ussher, James, Hinks, Timothy S.C., Marchi, Emanuele, Willberg, Chris, Klenerman, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899450/
https://www.ncbi.nlm.nih.gov/pubmed/31533032
http://dx.doi.org/10.1016/j.celrep.2019.08.050
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author Leng, Tianqi
Akther, Hossain Delowar
Hackstein, Carl-Philipp
Powell, Kate
King, Thomas
Friedrich, Matthias
Christoforidou, Zoe
McCuaig, Sarah
Neyazi, Mastura
Arancibia-Cárcamo, Carolina V.
Hagel, Joachim
Powrie, Fiona
Peres, Raphael Sanches
Millar, Val
Ebner, Daniel
Lamichhane, Rajesh
Ussher, James
Hinks, Timothy S.C.
Marchi, Emanuele
Willberg, Chris
Klenerman, Paul
author_facet Leng, Tianqi
Akther, Hossain Delowar
Hackstein, Carl-Philipp
Powell, Kate
King, Thomas
Friedrich, Matthias
Christoforidou, Zoe
McCuaig, Sarah
Neyazi, Mastura
Arancibia-Cárcamo, Carolina V.
Hagel, Joachim
Powrie, Fiona
Peres, Raphael Sanches
Millar, Val
Ebner, Daniel
Lamichhane, Rajesh
Ussher, James
Hinks, Timothy S.C.
Marchi, Emanuele
Willberg, Chris
Klenerman, Paul
author_sort Leng, Tianqi
collection PubMed
description 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.
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spelling pubmed-68994502020-01-21 TCR and Inflammatory Signals Tune Human MAIT Cells to Exert Specific Tissue Repair and Effector Functions Leng, Tianqi Akther, Hossain Delowar Hackstein, Carl-Philipp Powell, Kate King, Thomas Friedrich, Matthias Christoforidou, Zoe McCuaig, Sarah Neyazi, Mastura Arancibia-Cárcamo, Carolina V. Hagel, Joachim Powrie, Fiona Peres, Raphael Sanches Millar, Val Ebner, Daniel Lamichhane, Rajesh Ussher, James Hinks, Timothy S.C. Marchi, Emanuele Willberg, Chris Klenerman, Paul Cell Rep Article 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. Cell Press 2019-09-17 /pmc/articles/PMC6899450/ /pubmed/31533032 http://dx.doi.org/10.1016/j.celrep.2019.08.050 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Leng, Tianqi
Akther, Hossain Delowar
Hackstein, Carl-Philipp
Powell, Kate
King, Thomas
Friedrich, Matthias
Christoforidou, Zoe
McCuaig, Sarah
Neyazi, Mastura
Arancibia-Cárcamo, Carolina V.
Hagel, Joachim
Powrie, Fiona
Peres, Raphael Sanches
Millar, Val
Ebner, Daniel
Lamichhane, Rajesh
Ussher, James
Hinks, Timothy S.C.
Marchi, Emanuele
Willberg, Chris
Klenerman, Paul
TCR and Inflammatory Signals Tune Human MAIT Cells to Exert Specific Tissue Repair and Effector Functions
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899450/
https://www.ncbi.nlm.nih.gov/pubmed/31533032
http://dx.doi.org/10.1016/j.celrep.2019.08.050
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