Lack of gamma delta T cells ameliorates inflammatory response after acute intestinal ischemia reperfusion in mice

Abstract

T-cells have been demonstrated to modulate ischemia–reperfusion injury (IRI) in the kidney, lung, liver, and intestine. Whereas most T-cell subpopulations contribute primarily to the antigen-specific effector and memory phases of immunity, γδ-T-cells combine adaptive features with rapid, innate-like responses that can place them in the initiation phase of immune reactions. Therefore, we aimed to clarify the role of γδ-T-cells in intestinal IRI. Adult wild-type (WT) and γδ-T-cell-deficient mice were subjected to acute intestinal IRI. Gene expression of pro-inflammatory cytokines and influx of leukocyte subpopulations in the gut were assessed by qPCR and flow cytometry. Serum transaminases were measured as an indicator of distant organ IRI. Intestinal IRI led to increased influx of neutrophils, pro-inflammatory cytokine expression and LDH/ALT/AST elevation. Selective deficiency of γδ-T-cells significantly decreased pro-inflammatory cytokine levels and neutrophil infiltration in the gut following IRI compared to controls. Furthermore, γδ-T-cell deficiency resulted in decreased LDH and transaminases levels in sera, indicating amelioration of distant organ injury. Increasing evidence demonstrates a key role of T-cell subpopulations in IRI. We demonstrate that γδ-T-cell deficiency ameliorated pro-inflammatory cytokine production, neutrophil recruitment and distant organ injury. Thus, γδ-T-cells may be considered as mediators contributing to the inflammatory response in the acute phase of intestinal IRI.

The role of γδ T17 cells in cardiovascular disease

“…Selective depletion of γδ T cells after IRI significantly reduced proinflammatory cytokine levels and neutrophil infiltration in the intestinal tract compared with the control group. 196 In addition, γδ T KO delayed inflammatory reaction in early renal IRI, but with the extension of reperfusion time, the survival rate of knockout mice decreased. 194,197,198…”

“…Importantly, recent studies in other IRI models also show that γδ T17 cells have a vital contribution to IRI 65,66,194–196 . For example, γδ T cells can be considered as mediators promoting the inflammatory response in the acute stage of intestinal IRI.…”

“…Importantly, recent studies in other IRI models also show that γδ T17 cells have a vital contribution to IRI. 65,66,[194][195][196] For example, γδ T cells can be considered as mediators promoting the inflammatory response in the acute stage of intestinal IRI. Selective depletion of γδ T cells after IRI significantly reduced proinflammatory cytokine levels and neutrophil infiltration in the intestinal tract compared with the control group.…”

Faecal Microbiota Transplantation and Chronic Kidney Disease

“…Wang et al found that neutrophils and macrophages were recruited and activated as part of the first-line immune response in innate immunity against kidney disease induced by adenine in mice [63]. Moreover, Funken et al identified that the γδ-T cells as potent mediators in ischemia-reperfusion injury (IRI) contributed to the increased influx of neutrophils and pro-inflammatory cytokines, which were not found in δ-T cell deficiency mice [64]. IRI mouse model induced by bilateral renal pedicle clamping resulted in altered gut bacterial dysbiosis resulting in significant decreases in Lactobacilli, Ruminococacceae, and an increase in Enterobacteriaceae.…”

Organized Chaos: Deciphering Immune Cell Heterogeneity’s Role in Inflammation in the Heart

“…In murine models, gamma delta T-cells are found within the infarct as early as Day 1 post-MI and peak at Day 7 post-MI [ 95 ]. Funken et al found that the loss of gamma delta T-cells in mice helped improve organ injury [ 96 ]. Through a gamma delta T-cell genetic depletion mouse model, Caillon et al discovered that this T-cell subset may also mediate vascular injury and activation of other T-cell subsets thus fostering an exacerbation of inflammation [ 97 ].…”