Dermal γδ T-Cells Can Be Activated by Mitochondrial Damage-Associated Molecular Patterns

• Published in: PloS one Vol. 11; no. 7; p. e0158993
• Main Authors: Schwacha, Martin G, Rani, Meenakshi, Nicholson, Susannah E, Lewis, Aaron M, Holloway, Travis L, Sordo, Salvador, Cap, Andrew P
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-07-2016; Public Library of Science (PLoS)
• Subjects: Animals; Apoptosis; Biology and Life Sciences; Burns; Burns - immunology; Burns - pathology; Centrifugation; Chemokines; Cytokines; Cytokines - biosynthesis; Damage patterns; Gene Expression Regulation; Growth factors; Immune system; Inflammation; Inflammatory response; Injuries; Intercellular Signaling Peptides and Proteins - biosynthesis; Interleukin 6; Laboratory animals; Liver - pathology; Lymphocytes; Lymphocytes T; Male; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Mitochondria; Mitochondria - pathology; Mitochondrial DNA; Ostomy; Platelet-derived growth factor; Proteins; Receptors; Receptors, Antigen, T-Cell, gamma-delta - metabolism; Research and Analysis Methods; Science; Skin; Skin - immunology; Sonication; Surgery; T cell receptors; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; TLR2 protein; TLR4 protein; Toll-like receptors; Toll-Like Receptors - metabolism; Trauma; Vascular endothelial growth factor; Wound healing; United States > US; Texas
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0158993

Gamma delta T-cells have been shown to be important to the early immunoinflammatory response to injury, independent of infection. This unique T-cell population acts to regulate cell trafficking and the release of cytokines and growth factors. We propose this sterile inflammatory response is in part associated with damage associated molecular patterns (DAMPs) generated by major injury, such as burn, and mediated via toll-like receptors (TLRs). It is unknown whether DAMPs can activate resident γδ T-cells that reside in skin.
Gamma delta T-cells were isolated from the skin of male C57BL/6 mice by enzymatic digestion. Mitochondrial DAMPs (MTDs) were generated from mitochondria isolated from mouse livers by sonication and centrifugation. Dermal γδ T-cells were incubated with MTDs (0-500 μg/ml) for 24 hr and cells and supernatants were collected for analysis.
MTDs activated dermal γδ T-cells, as evidenced by increased TLR2 and TLR4 expression following in vitro exposure. MTDs also induced the production of inflammatory cytokines (IL-1β, IL-6), and growth factors (PDGF and VEGF) by γδ T-cells.
These findings herein support the concept that MTDs released after tissue/cellular injury are capable of activating dermal γδ T-cells. We propose that the activation of this unique T-cell population is central in the initiation of sterile inflammation and also contributes to the subsequent healing processes.