γδ T-cells: Potential regulators of the post-burn inflammatory response

Schwacha, Martin G.

doi:10.1016/j.burns.2008.08.002

Cited by 35 publications

(53 citation statements)

References 110 publications

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“…γδ T cells regulate proinflammatory cytokine production by multiple immune cell subsets (24) and suppress cytotoxic T-cell activity against both tumor cells (25) and foreign antigens (26). In human burn wounds, γδ T cells hyper-activate macrophages (27), and therefore a potential role of γδ T cells in InvEE mice may be to attract macrophages (28,29). This would be consistent with the reduction in the number of monocytes in InvEE skin following reconstitution by TCRδ −/− bone marrow (Fig.…”

Section: Discussionsupporting

confidence: 72%

Tumor formation initiated by nondividing epidermal cells via an inflammatory infiltrate

Arwert

Lal

Quist

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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In mammalian epidermis, integrin expression is normally confined to the basal proliferative layer that contains stem cells. However, in epidermal hyperproliferative disorders and tumors, integrins are also expressed by suprabasal cells, with concomitant up-regulation of Erk mitogen-activated protein kinase (MAPK) signaling. In transgenic mice, expression of activated MAPK kinase 1 (MEK1) in the suprabasal, nondividing, differentiated cell layers (InvEE transgenics) results in epidermal hyperproliferation and skin inflammation. We now demonstrate that wounding induces benign tumors (papillomas and keratoacanthomas) in InvEE mice. By generating chimeras between InvEE mice and mice that lack the MEK1 transgene, we demonstrate that differentiating, nondividing cells that express MEK1 stimulate adjacent transgene-negative cells to divide and become incorporated into the tumor mass. Dexamethasone treatment inhibits tumor formation, suggesting that inflammation is involved. InvEE skin and tumors express high levels of IL1α; treatment with an IL1 receptor antagonist delays tumor onset and reduces incidence. Depletion of γδ T cells and macrophages also reduces tumor incidence. Because a hallmark of cancer is uncontrolled proliferation, it is widely assumed that tumors arise only from dividing cells. In contrast, our studies show that differentiated epidermal cells can initiate tumor formation without reacquiring the ability to divide and that they do so by triggering an inflammatory infiltrate.cancer | differentiation

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Section: Discussionsupporting

confidence: 72%

Tumor formation initiated by nondividing epidermal cells via an inflammatory infiltrate

Arwert

Lal

Quist

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…30 Studies from our laboratory have established an important role of γ δ T-cells in burn-induced immunopathology influencing macrophage function, distal organ injury and wound repair. 17,18,31-33 Importantly, we observed that γδ T-cells are important in the recruitment of inflammatory cells to the injury site after burn, as γ δ T-cell deficient mice displayed a significant reduction in the cellular filtrate. 31 While in the study herein we have observed that the total number of T-cells at the burn wound site increases and are predominantly α β T-cells, concurrent findings have shown that the α β T-cell influx was dependent upon the presence of γ δ T-cells, as this T-cell infiltration of the wound site was not evident in mice deficient in γ δ T-cells.…”

Section: Discussionmentioning

confidence: 80%

“…15,16 Our studies have also clearly demonstrated that γδ T-cells, are central in the response to burn injury. 17,18 Nonetheless, the relationship of γδ T-cells to T-cell cytokine responses at the injury site after burn remains unidentified.…”

Section: Introductionmentioning

confidence: 99%

Burn Wound γδ T-Cells Support a Th2 and Th17 Immune Response

Rani

Zhang

Schwacha

2014

Journal of Burn Care & Research

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Objectives Major burn triggers immune dysfunction, which is associated with wound healing complications. Gamma delta T-cells have been shown to be important in post-burn inflammation and wound healing; however their cytokine phenotype at the burn wound site is unknown. Methods C57BL/6 male mice were subjected to a major burn (25% TBSA, 3rd degree) or sham treatment. At 3 h, 3 days and 7 days thereafter, skin samples were collected and subjected to dispase and trypsin digestion to isolate single cells. The cells were phenotyped and evaluated for cytokine profiles by flow cytometry. Th-1 cells were defined as IFNγ positive, Th-2 cells were defined IL-10 positive and Th-17 cells were defined as IL-17 positive. Results At 7 days after burn a shift towards Th-2 and Th-17 positive T-cells at the wound site was observed. Further analysis revealed that at 3 h post-injury the percentage of γδ T-cells positive for IFNγ, IL-10 and IL-17 where comparable between sham and burn skin samples. At 3 days and 7 days post-injury the percentage of cells positive for each cytokine increased; however, the increase was significantly greater for IL-10 and IL-17, as compared with IFNγ (i.e., 9-20 fold vs. 3-fold). Skin αβ T-cells preferentially produced IFNγ (~20%), which was unaffected by burn injury. Conclusions These data demonstrate that burn wound γδ T-cells are activated for enhanced cytokine production and display a shift towards a Th-2 and/or Th-17 phenotype. In contrast, burn wound αβ T-cells were not activated for enhanced cytokine production.

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“…NO has exhibited a role in fibroblast proliferation, collagen synthesis 33 and contraction of collagen lattices. 34 Also macrophage angiogenic activity (important for wound healing) is dependent on NO synthase, 34 and NO synthase activity is upregulated in tendinopathy. 35 However, one can doubt whether sufficient absorption of NO through the skin and into the degenerative area of the tendon occurs.…”

Section: Discussionmentioning

confidence: 99%

Topical glyceryl trinitrate treatment of chronic patellar tendinopathy: a randomised, double-blind, placebo-controlled clinical trial

Steunebrink¹,

Zwerver

Brandsema

et al. 2012

Br J Sports Med

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ObjectivesTo assess if continuous topical glyceryl trinitrate (GTN) treatment improves outcome in patients with chronic patellar tendinopathy when compared with eccentric training alone.MethodsRandomised double-blind, placebo-controlled clinical trial comparing a 12-week programme of using a GTN or placebo patch in combination with eccentric squats on a decline board. Measurements were performed at baseline, 6, 12 and 24 weeks. Primary outcome measure was the Victorian Institute of Sports Assessment-Patella (VISA-P) questionnaire. Secondary outcome measures were patient satisfaction and pain scores during sports. Generalised estimated equation was used to analyse the treatment, time and treatment×time effect. Analyses were performed following the intention-to-treat principle.ResultsVISA-P scores for both groups improved over the study period to 75.0±16.2 and 80.7±22.1 at 24 weeks. Results showed a significant effect for time (p<0.01) but no effect for treatment×time (p=0.80). Mean Visual Analogue Scores pain scores during sports for both groups increased over the study period to 6.6±3 and 7.8±3.1. Results showed a significant effect for time (p<0.01) but no effect for treatment×time (p=0.38). Patient satisfaction showed no difference between GTN and placebo groups (p=0.25) after 24 weeks, but did show a significant difference over time (p=0.01). Three patients in the GTN group reported some rash.ConclusionIt seems that continuous topical GTN treatment in addition to an eccentric exercise programme does not improve clinical outcome compared to placebo patches and an eccentric exercise programme in patients with chronic patellar tendinopathy.

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γδ T-cells: Potential regulators of the post-burn inflammatory response

Cited by 35 publications

References 110 publications

Tumor formation initiated by nondividing epidermal cells via an inflammatory infiltrate

Tumor formation initiated by nondividing epidermal cells via an inflammatory infiltrate

Burn Wound γδ T-Cells Support a Th2 and Th17 Immune Response

Topical glyceryl trinitrate treatment of chronic patellar tendinopathy: a randomised, double-blind, placebo-controlled clinical trial

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