T-Lymphocytes Modulate the Microvascular and Inflammatory Responses to Intestinal Ischemia-Reperfusion

Shigematsu, Tomohiro; Wolf, Robert; Granger, D Neil

doi:10.1038/sj.mn.7800126

Cited by 36 publications

(39 citation statements)

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“…However, our data demonstrates that, in the first hours following intestinal IR, αβ T cells do not significantly contribute to the acute injury. Our findings are seemingly in opposition to existing studies that have suggested an involvement of T cells in intestinal IRI: Studies in SCID mice demonstrated protection from intestinal IRI [14,27,33]. Shigematsu and colleagues reported a significant reduction in the intestinal leakage of albumin compared to the WT and restoration of the WT levels of albumin extravasation was reported in SCID mice reconstituted with T cells from WT mice.…”

Section: Discussioncontrasting

confidence: 99%

“…The effects observed in that study were rather mild with a relative change of 10% and the applied reperfusion time with 6 hours longer than in our model, thus may explaining the minor differences between their findings and that of the current study [13]. Nevertheless, the question of the T cell influx in intestinal IRI remain unresolved as influx kinetics in the literature are discrepant: One further study showed an increase of CD4 + (αβ) T cells in the gut 1h after ischemia (but not after 3 hours of reperfusion) compared to control mice, while another found no difference 1 hour after reperfusion but a peak of T cells after 6 hours of reperfusion [14,27]. We assume that the different mouse strains and different methodological approaches utilized in these studies may account for the inconsistencies.…”

Section: Discussionmentioning

confidence: 72%

“…Tissue myeloperoxidase activity was also significantly decreased in the SCID mice when compared to WT. The authors concluded that (all types of) T cells are important for recruitment of neutrophils and that T cells have a pathogenic effect during intestinal IRI [14]. Likewise, Edgerton et al show amelioration in another strain of SCID mice, reconstitution of tissue damage following repletion of T cells, and mitigation of injury following anti-CD4-antibody treatment [27].…”

Section: Discussionmentioning

confidence: 99%

“…Shigematsu et al found a reduction of myeloperoxidase activity by ~66% following IRI. Therefore, we determined a relevant effect to be the reduction of neutrophils of at least 50% as the primary endpoint resulting in a calculated group size of n = 6 (Power 0,931, Difference in Means 0,500, Standard Deviation 0,200, Number of Groups 4, Alpha 0,0500) [14]. One-way analysis of variance with a Tukey’s multiple comparisons test was performed with GraphPad Prism v6.0 (GraphPad Software, San Diego, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…The few published studies that have assessed lymphocytes in intestinal IRI have demonstrated that various T cell subpopulations infiltrate the gut following IR [13]. Functional studies on SCID mice or mice treated with anti-thymocyte globulin (ATG) suggested an amelioration of intestinal IRI by lack of T cells or their inhibition, respectively [14,15]. However, SCID mice also lack non-conventional γδ T cells, B cells, and the immunoglobulins that are crucial for complement activation, while ATG has a broad range of targets apart from T cells [16].…”

Section: Introductionmentioning

confidence: 99%

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Conventional alpha beta (αβ) T cells do not contribute to acute intestinal ischemia-reperfusion injury in mice

Vieten

et al. 2017

PLoS ONE

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PurposeIschemia-reperfusion injury (IRI) is associated with significant patient mortality and morbidity. The complex cascade of IRI is incompletely understood, but inflammation is known to be a key mediator. In addition to the predominant innate immune responses, previous research has also indicated that αβ T cells contribute to IRI in various organ models. The aim of this study was to clarify the role αβ T cells play in IRI to the gut.MethodsAdult wild-type (WT) and αβ T cell-deficient mice were subjected to acute intestinal IRI with 30min ischemia followed by 4h reperfusion. The gene expression of pro-inflammatory cytokines was measured by qPCR, and the influx of leukocyte subpopulations in the gut was assessed via flow cytometry and histology. Pro-inflammatory cytokines in the serum were measured, and transaminases were assessed as an indicator of distant organ IRI.ResultsIntestinal IRI led to an increased expression of pro-inflammatory cytokines in the gut tissue and an influx of leukocytes that predominantly consisted of neutrophils and macrophages. Furthermore, intestinal IRI increased serum IL-6, TNF-α, and ALT/AST levels. The αβ T cell-deficient mice did not exhibit a more significant increase in pro-inflammatory cytokines in the gut or serum following IR than the WT mice. There was also no difference between WT- and αβ T cell-deficient mice in terms of neutrophil infiltration or macrophage activation. Furthermore, the increase in transaminases was equal in both groups indicating that the level of distant organ injury was comparable.ConclusionAn increasing body of evidence demonstrates that αβ T cells play a key role in IRI. In the gut, however, αβ T cells are not pivotal in the first hours following acute IRI as deficiency does not impact cytokine production, neutrophil recruitment, macrophage activation, or distant organ injury. Thus, αβ T cells may be considered innocent bystanders during the acute phase of intestinal IRI.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Conventional alpha beta (αβ) T cells do not contribute to acute intestinal ischemia-reperfusion injury in mice

Vieten

et al. 2017

PLoS ONE

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Wielding the Double‐Edged Sword of Inflammation: Building Biomaterial‐Based Strategies for Immunomodulation in Ischemic Stroke Treatment

Khait

Shoichet

2021

Adv Funct Materials

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Stroke is a leading cause of disability with no current treatment to regenerate lost brain tissue. Innovative preclinical and clinical trials have attempted to improve stroke recovery by promoting cell survival, downregulating astrogliosis and inflammation, and improving neurogenesis and angiogenesis; however, the complexity of stroke pathophysiology raises many challenges. Previous attempts to grossly inhibit the inflammatory reaction failed to improve stroke outcomes, prompting scientists to explore selective modulation rather than unbiased inhibition. Although experimental studies involving immunomodulation are successful, strategies have largely failed in the clinic. Some of these approaches are hindered by poor delivery efficiency or cell survival, challenges that could be at least partially overcome using biomaterials. Biomaterials may enhance immunomodulatory processes by improving drug and cell delivery to the injured tissue. Furthermore, the materials themselves can support healing and may be designed to act as immunomodulators, thereby contributing to tissue regeneration and endogenous repair processes. Described here are novel biomaterial-based strategies to modulate the immune response after ischemic stroke, with an emphasis on extracellular matrix mimetics and hydrogels for local delivery of drugs and cells. Finally, a future perspective is described, highlighting the potential of these therapies to achieve clinical translation and improve patients' functional repair.

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Cyclical ischaemic preconditioning modulates the adaptive immune response in human limb ischaemia–reperfusion injury

Sullivan

Sweeney

Hirpara

et al. 2009

British Journal of Surgery

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T-Lymphocytes Modulate the Microvascular and Inflammatory Responses to Intestinal Ischemia-Reperfusion

Cited by 36 publications

References 0 publications

Conventional alpha beta (αβ) T cells do not contribute to acute intestinal ischemia-reperfusion injury in mice

Conventional alpha beta (αβ) T cells do not contribute to acute intestinal ischemia-reperfusion injury in mice

Wielding the Double‐Edged Sword of Inflammation: Building Biomaterial‐Based Strategies for Immunomodulation in Ischemic Stroke Treatment

Cyclical ischaemic preconditioning modulates the adaptive immune response in human limb ischaemia–reperfusion injury

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