TCR and inflammatory signals tune human MAIT cells to exert specific tissue repair and effector functions
| Autor: | Leng, Tianqi, Akther, Hossain Delowar, Hackstein, Carl-Philipp, King, Thomas, Friedrich, Matthias, Christoforidou, Zoe, McCuaig, Sarah, Neyazi, Mastura, Arancibia-Cárcamo, Carolina V., Powrie, Fiona, Marchi, Emanuele, Peres, Raphael Sanches, Millar, Val, Ebner, Danie, Willberg, Chris, Klenerman, Paul |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0303 health sciences
education.field_of_study Effector medicine.medical_treatment T cell Population T-cell receptor Biology Cell biology 03 medical and health sciences 0302 clinical medicine Cytokine medicine.anatomical_structure In vivo Gene expression medicine education Tissue homeostasis 030304 developmental biology 030215 immunology |
| DOI: | 10.1101/475913 |
| Popis: | SUMMARYMAIT cells are an abundant T-cell population enriched in peripheral tissues such as the liver. They are activated both through TCR-dependent and - independent mechanisms. However, the different specific functional responses of MAIT cells to these distinct signals remain elusive. We examined the impact of combinations of TCR-dependent and -independent signals in blood and tissue-derived human MAIT cells. TCR-independent activation of MAIT cells from blood and gut was maximised by extending the panel of cytokines to including TNF-superfamily member TL1A. RNAseq experiments revealed that TCR-dependent and -independent signals drive MAIT cells to exert overlapping and unique effector functions, impacting both host defence and tissue homeostasis. While TCR-triggering alone is insufficient to drive sustained activation, TCR-triggered MAIT cells did show specific enrichment of tissue-repair functions at the level of gene expression, protein production and in in vitro assays and these functions were amplified by cytokine costimulation. Taken together, these data indicate the blend of TCR-dependent and -independent signalling to MAIT cells may play a role in controlling the balance between healthy and pathological processes of tissue inflammation and repair. |
| Databáze: | OpenAIRE |
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