title: Dermal γδ T-Cells Can Be Activated by Mitochondrial Damage-Associated Molecular Patterns.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, The University of Texas Health Science Center at San Antonio, Texas, United States of America.|Blood Research, United States Army Institute of Surgical Research, Fort Sam Houston, Texas, United States of America.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Schwacha
authors.affiliation: Department of Surgery, The University of Texas Health Science Center at San Antonio, Texas, United States of America.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Rani
authors.affiliation: Department of Surgery, The University of Texas Health Science Center at San Antonio, Texas, United States of America.
authors.forename: Susannah E
authors.initials: SE
authors.lastname: Nicholson
authors.affiliation: Department of Surgery, The University of Texas Health Science Center at San Antonio, Texas, United States of America.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Lewis
authors.affiliation: Department of Surgery, The University of Texas Health Science Center at San Antonio, Texas, United States of America.
authors.forename: Travis L
authors.initials: TL
authors.lastname: Holloway
authors.affiliation: Department of Surgery, The University of Texas Health Science Center at San Antonio, Texas, United States of America.
authors.forename: Salvador
authors.initials: S
authors.lastname: Sordo
authors.affiliation: Department of Surgery, The University of Texas Health Science Center at San Antonio, Texas, United States of America.|Blood Research, United States Army Institute of Surgical Research, Fort Sam Houston, Texas, United States of America.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Cap
mesh_terms: D000818:Animals; D002056:Burns / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D005786:Gene Expression Regulation; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000473:pathology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D012867:Skin / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D051193:Toll-Like Receptors