Dermal γδ T-cells can be activated by mitochondrial damage-associated molecular patterns

Martin G Schwacha, Meenakshi Rani, Susannah E. Nicholson, Aaron M. Lewis, Travis L. Holloway, Salvador Sordo, Andrew P. Cap

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere0158993
JournalPLoS One
Volume11
Issue number7
DOIs
StatePublished - Jul 1 2016

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T-cells
T-lymphocytes
T-Lymphocytes
Skin
Somatostatin-Secreting Cells
skin (animal)
growth factors
Intercellular Signaling Peptides and Proteins
Wounds and Injuries
cytokines
inflammation
Cytokines
Sonication
Mitochondria
Centrifugation
Toll-Like Receptors
mice
interleukin-1
Interleukin-1
Inbred C57BL Mouse

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Schwacha, M. G., Rani, M., Nicholson, S. E., Lewis, A. M., Holloway, T. L., Sordo, S., & Cap, A. P. (2016). Dermal γδ T-cells can be activated by mitochondrial damage-associated molecular patterns. PLoS One, 11(7), [e0158993]. https://doi.org/10.1371/journal.pone.0158993

Dermal γδ T-cells can be activated by mitochondrial damage-associated molecular patterns. / Schwacha, Martin G; Rani, Meenakshi; Nicholson, Susannah E.; Lewis, Aaron M.; Holloway, Travis L.; Sordo, Salvador; Cap, Andrew P.

In: PLoS One, Vol. 11, No. 7, e0158993, 01.07.2016.

Research output: Contribution to journalArticle

Schwacha, MG, Rani, M, Nicholson, SE, Lewis, AM, Holloway, TL, Sordo, S & Cap, AP 2016, 'Dermal γδ T-cells can be activated by mitochondrial damage-associated molecular patterns', PLoS One, vol. 11, no. 7, e0158993. https://doi.org/10.1371/journal.pone.0158993
Schwacha, Martin G ; Rani, Meenakshi ; Nicholson, Susannah E. ; Lewis, Aaron M. ; Holloway, Travis L. ; Sordo, Salvador ; Cap, Andrew P. / Dermal γδ T-cells can be activated by mitochondrial damage-associated molecular patterns. In: PLoS One. 2016 ; Vol. 11, No. 7.
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