Mitochondrial damage-associated molecular patterns activate γδ T-cells
- 11 June 2013
- journal article
- research article
- Published by SAGE Publications in Innate Immunity
- Vol. 20 (3), 261-268
- https://doi.org/10.1177/1753425913488969
Abstract
Gamma delta T-cells have been shown to be important in the early immunoinflammatory response to injury, which can be independent of infection. This sterile inflammatory response is believed to be, in part, associated with danger-associated molecular patterns (DAMPs). Mitochondrial DAMPs (MTDs) have been shown to be important in trauma-induced neutrophil activation, but it is unknown whether MTDs activate other innate immune cells, such as γδ T-cells. To study this, splenic CD3+ γδ T-cells were isolated from αβ T-cell-deficient C57BL/6 mice and mitochondria isolated from wild type mouse livers. MTDs were isolated from mitochondria by sonication and centrifugation. Gamma delta T-cells were incubated with various concentrations of MTDs (0–500 µg/ml) for 24 h. T-cells were phenotyped for TLR expression by flow cytometry and the supernatants assayed for cytokine and growth factor content. MTDs caused a dose-dependent increase in TLR2 and TLR4 expression by γδ T-cells. Both the percentage of cells positive for TLRs and the degree of expression increased. MTDs also induced the production of IL-1β, IL-6, IL-10, RANTES, fibroblast growth factor-basic and vascular endothelial growth factor by γδ T-cells. These findings support the concept that the MTDs released after tissue/cellular injury are capable of activating γδ T-cells, thus initiating sterile inflammation, as well as subsequent healing processes.Keywords
This publication has 41 references indexed in Scilit:
- IL‐17‐producing γδ T cells and innate lymphoid cellsEuropean Journal of Immunology, 2012
- Trauma is dangerJournal of Translational Medicine, 2011
- IL-17A-Producing gamma delta T and Th17 Lymphocytes Mediate Lung Inflammation but Not Fibrosis in Experimental SilicosisThe Journal of Immunology, 2010
- Circulating mitochondrial DAMPs cause inflammatory responses to injuryNature, 2010
- Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasomeProceedings of the National Academy of Sciences of the United States of America, 2009
- Adoptively transferred ex vivo expanded γδ-T cells mediate in vivo antitumor activity in preclinical mouse models of breast cancerBreast Cancer Research and Treatment, 2009
- γδ T-cells: Potential regulators of the post-burn inflammatory responseBurns, 2009
- Up-regulation of cell surface Toll-like receptors on circulating γδ T-cells following burn injuryCytokine, 2008
- REGULATION OF THE POSTBURN WOUND INFLAMMATORY RESPONSE BY γδ T-CELLSShock, 2007
- Cutaneous Wound HealingNew England Journal of Medicine, 1999