Ischemia–reperfusion and immediate T cell responses

Huang, Yanfei; Rabb, Hamid; Womer, Karl L.

doi:10.1016/j.cellimm.2007.03.009

Cited by 132 publications

(93 citation statements)

References 90 publications

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“…Physiological stress and the subsequent activation of the neurohormonal system during STEMI leads to cortisol release, which in turn mediates lymphopenia through apoptosis [20]. Atherosclerosis and plaque rupture leading to ACS is an inflammatory process mediated by the complex interplay between the innate neutrophil mediated reactive immune responses, and subsequent lymphocyte mediated adaptive immune responses [5][6][7]. Thus, NLR may act as a combined surrogate marker for both the reactive and adaptive components of the inflammatory response that result in plaque rupture, ischemic myocardial damage, adverse ventricular remodeling, and consequent left ventricular dysfunction.…”

Section: Discussionmentioning

confidence: 99%

“…NLR is a surrogate marker for the combined effects of the innate immune response (substantially mediated by neutrophils), and the subsequent adaptive immune response (substantially mediated by lymphocytes). NLR may also reflect the myocardial remodeling responses after reperfusion injury [5][6][7]. Nevertheless, the role of NLR in predicting short-and long-term mortality after ST-segment elevation myocardial infarction (STEMI), treated with primary percutaneous coronary intervention (PCI) in the drug eluting stent era remains undefined.…”

Section: Introductionmentioning

confidence: 99%

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Neutrophil to lymphocyte ratio predicts short- and long-term mortality following revascularization therapy for ST elevation myocardial infarction

et al. 2014

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(OR = 5.35, p < 0.001), cerebrovascular accident history (OR = 3.36, p = 0.023), low glomerular filtration rate (OR = 0.98, p = 0.012) and cardiac arrest on admission (OR = 17.43, p < 0.001) as robust independent predictors of long-term mortality. NLR was divided into two sub-groups based on an optimal cut off value of 7.4. This provided the best discriminatory cut off point for predicting adverse mortality outcome. (Cardiol J 2014; 21, 5: 500-508)

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neutrophil to lymphocyte ratio predicts short- and long-term mortality following revascularization therapy for ST elevation myocardial infarction

et al. 2014

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“…1,2 Dendritic cells (DCs), the major subset of leukocytes in the kidney, [3][4][5] contribute to innate and adaptive immunity of kidney IRI 6 through activation of immune cells. [7][8][9] Considerable data suggest that the immune system mediates AKI, and anti-inflammatory treatments significantly attenuate tissue injury and loss of function. However, the side effects of common anti-inflammatory therapies combined with the lack of clinical data, supporting the involvement of the immune system in AKI pathogenesis, have hindered the development of anti-inflammatory options.…”

mentioning

confidence: 99%

Sphingosine 1-Phosphate Receptor 3–Deficient Dendritic Cells Modulate Splenic Responses to Ischemia-Reperfusion Injury

Bajwa

Huang

Kurmaeva

et al. 2016

Journal of the American Society of Nephrology

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The plasticity of dendritic cells (DCs) permits phenotypic modulation ex vivo by gene expression or pharmacologic agents, and these modified DCs can exert therapeutic immunosuppressive effects in vivo through direct interactions with T cells, either inducing T regulatory cells (T REG s) or causing anergy. Sphingosine 1-phosphate (S1P) is a sphingolipid and the natural ligand for five G protein-coupled receptors (S1P1, S1P2, S1P3, S1P4, and S1P5), and S1PR agonists reduce kidney ischemia-reperfusion injury (IRI) in mice. S1pr3 2/2 mice are protected from kidney IRI, because DCs do not mature. We tested the therapeutic advantage of S1pr3 2/2 bone marrow-derived dendritic cell (BMDC) transfers in kidney IRI. IRI produced a rise in plasma creatinine (PCr) levels in mice receiving no cells (NCs) and mice pretreated with wild-type (WT) BMDCs. However, S1pr3 2/2 BMDC-pretreated mice were protected from kidney IRI. S1pr3 2/2BMDC-pretreated mice had significantly higher numbers of splenic T REG s compared with NC and WT BMDC-pretreated mice. S1pr3 2/2 BMDCs did not attenuate IRI in splenectomized, Rag-1 2/2 , or CD11c + DC-depleted mice. Additionally, S1pr3 2/2 BMDC-dependent protection required CD169 + marginal zone macrophages and the macrophage-derived chemokine CCL22 to increase splenic CD4 + Foxp3 + T REG s.Pretreatment with S1pr3 2/2 BMDCs also induced T REG -dependent protection against IRI in an allogeneic mouse model. In summary, adoptively transferred S1pr3 2/2 BMDCs prevent kidney IRI through interactions within the spleen and expansion of splenic CD4 + Foxp3 + T REG s. We conclude that genetically induced deficiency of S1pr3 in allogenic BMDCs could serve as a therapeutic approach to prevent IRI-induced AKI.

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“…1,2 CD4 + T cell is a key player in the pathogenesis of renal IRI. 3,4 T cell deficiency results in resistance to renal IRI, which can be restored by the adoptive transfer of CD4 + T cells. 5,6 CD4 + T cells consist of functionally distinct subsets including conventional T cells and natural killer T (NKT) cells.…”

mentioning

confidence: 99%

Hypoxia-Inducible Factor-2α Limits Natural Killer T Cell Cytotoxicity in Renal Ischemia/Reperfusion Injury

Zhang

Han

Dai

et al. 2016

Journal of the American Society of Nephrology

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Natural killer T (NKT) cells are the major early-acting immune cell type and fundamental immune modulators in ischemia-reperfusion injury (IRI). Because lymphocytes are exposed to various oxygen tensions under pathophysiologic conditions, we hypothesize that hypoxia-inducible factors (HIFs) have roles in NKT cell activation, and thus determine the final outcome of renal IRI. In this study, we used Lck-Cre transgenic mice to specifically disrupt HIF-2a in T/NKT cells and found that HIF-2a knockout led to upregulated Fas ligand expression on peripheral NKT cells, but not on conventional T cells. HIF-2a knockout promoted infiltration of NKT cells into ischemic kidneys and exacerbated IRI, which could be mitigated by in vivo NK1.1 + cell depletion or Fas ligand blockade.Compared with wild-type NKT cells, HIF-2a 2/2 NKT cells adoptively transferred to Rag1-knockout mice elicited more severe renal injury, and these mice were not protected by CGS21680, an adenosine A2A receptor agonist. Mechanistically, hypoxia-induced expression of adenosine A2A receptor in NKT cells and CGS21680-induced cAMP production in thymocytes were HIF-2a-dependent. Hydrogen peroxide-induced Fas ligand expression on thymic wild-type NKT cells was significantly attenuated by CGS21680 treatment, but this effect was lost in HIF-2a 2/2 NKT cells. Finally, CGS21680 and LPS, an inducer of HIF-2a in endothelium, synergistically reduced renal IRI substantially, but this effect was absent in Mx1-Cre-induced global HIF-2a-knockout mice. Taken together, our results reveal a hypoxia/HIF-2a/adenosine A2A receptor axis that restricts NKT cell activation when confronted with oxidative stress and thus protects against renal IRI.

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Ischemia–reperfusion and immediate T cell responses

Cited by 132 publications

References 90 publications

Neutrophil to lymphocyte ratio predicts short- and long-term mortality following revascularization therapy for ST elevation myocardial infarction

Neutrophil to lymphocyte ratio predicts short- and long-term mortality following revascularization therapy for ST elevation myocardial infarction

Sphingosine 1-Phosphate Receptor 3–Deficient Dendritic Cells Modulate Splenic Responses to Ischemia-Reperfusion Injury

Hypoxia-Inducible Factor-2α Limits Natural Killer T Cell Cytotoxicity in Renal Ischemia/Reperfusion Injury

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