T Lymphocytes in Acute Kidney Injury and Repair

Fathabad, Somayeh Gharaie; Kurzhagen, Johanna T; Sadasivam, Mohanraj; Noel, Sanjeev; Bush, Errol L.; Hamad, Abdel R.A.; Rabb, Hamid

doi:10.1016/j.semnephrol.2020.01.003

Cited by 34 publications

(27 citation statements)

References 60 publications

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“…Adaptive immunity is mediated by T and B lymphocytes. Although there is some discrepancy, the majority of studies have demonstrated or suggested that CD4 + T cells are a factor in driving the initial phase of AKI in murine models, whereas the roles of cytotoxic T cells and B cells remain unclear [ 64 ]. Whether CD4 + T cells are involved in human AKI is unknown, but in pig models of renal autotransplantation, addition of polyethylene glycol, trimetazidine, and/or an inhibitor of complement to preservation solutions decreases infiltration of macrophages and T or CD4 + T cells into the kidney, and results in reduced graft injury [ 65–68 ].…”

Section: The Differences In Adaptive Immunity Among Rodents Large Anmentioning

confidence: 99%

“…Whether CD4 + T cells are involved in human AKI is unknown, but in pig models of renal autotransplantation, addition of polyethylene glycol, trimetazidine, and/or an inhibitor of complement to preservation solutions decreases infiltration of macrophages and T or CD4 + T cells into the kidney, and results in reduced graft injury [ 65–68 ]. Depending on inducers, CD4 + T cells can be activated and differentiated into different subsets including pro-inflammatory Th1 and Th17 cells and regulatory T cells (Treg) [ 64 ]. In rodents, both Th1 and Th17 subsets contribute to AKI through secreting pro-inflammatory cytokines and recruiting other types of pro-inflammatory cells into the kidney, whereas Treg cells protect the kidney from IRI and help resolution of AKI by limiting inflammation [ 64 , 69 , 70 ].…”

Section: The Differences In Adaptive Immunity Among Rodents Large Anmentioning

confidence: 99%

“…Depending on inducers, CD4 + T cells can be activated and differentiated into different subsets including pro-inflammatory Th1 and Th17 cells and regulatory T cells (Treg) [ 64 ]. In rodents, both Th1 and Th17 subsets contribute to AKI through secreting pro-inflammatory cytokines and recruiting other types of pro-inflammatory cells into the kidney, whereas Treg cells protect the kidney from IRI and help resolution of AKI by limiting inflammation [ 64 , 69 , 70 ].…”

Section: The Differences In Adaptive Immunity Among Rodents Large Anmentioning

confidence: 99%

“…Depending on experimental contexts, both reno-protective and reno-harmful effects of gut microbiota have been reported. Germ-free mice have an unexpectedly high frequency of natural killer T cells and abundant T cells in the kidney and are prone to I/R-induced AKI [ 64 ]. In contrary, depletion of mouse gut microbiota by an antibiotic-cocktail significantly attenuates I/R-induced AKI associated with low expression of F4/80 macrophages and pro-inflammatory chemokines [ 89 ].…”

Section: The Differences In Gut Microbiota Among Rodents Large Animamentioning

confidence: 99%

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Large animal models for translational research in acute kidney injury

et al. 2020

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While extensive research using animal models has improved the understanding of acute kidney injury (AKI), this knowledge has not been translated into effective treatments. Many promising interventions for AKI identified in mice and rats have not been validated in subsequent clinical trials. As a result, the mortality rate of AKI patients remains high. Inflammation plays a fundamental role in the pathogenesis of AKI, and one reason for the failure to translate promising therapeutics may lie in the profound difference between the immune systems of rodents and humans. The immune systems of large animals such as swine, nonhuman primates, sheep, dogs and cats, more closely resemble the human immune system. Therefore, in the absence of a basic understanding of the pathophysiology of human AKI, large animals are attractive models to test novel interventions. However, there is a lack of reviews on large animal models for AKI in the literature. In this review, we will first highlight differences in innate and adaptive immunities among rodents, large animals, and humans in relation to AKI. After illustrating the potential merits of large animals in testing therapies for AKI, we will summarize the current state of the evidence in terms of what therapeutics have been tested in large animal models. The aim of this review is not to suggest that murine models are not valid to study AKI. Instead, our objective is to demonstrate that large animal models can serve as valuable and complementary tools in translating potential therapeutics into clinical practice.

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Section: The Differences In Adaptive Immunity Among Rodents Large Anmentioning

confidence: 99%

Section: The Differences In Adaptive Immunity Among Rodents Large Anmentioning

confidence: 99%

Section: The Differences In Adaptive Immunity Among Rodents Large Anmentioning

confidence: 99%

Section: The Differences In Gut Microbiota Among Rodents Large Animamentioning

confidence: 99%

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Large animal models for translational research in acute kidney injury

et al. 2020

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“…A series of investigations have demonstrated an important role of T cells in the pathogenesis of AKI and repair [3]. However, it was puzzling why T cells were found in normal kidneys in the absence of disease.…”

Section: Immunity/inflammationmentioning

confidence: 99%

Gut Microbiome and AKI: Roles of the Immune System and Short-Chain Fatty Acids

Gharaie¹,

Noel²,

Rabb³

2020

Nephron

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Acute kidney injury (AKI) is a common and serious syndrome that involves multiple pathophysiologic mechanisms. Recent studies have demonstrated that dysbiosis of the gut microbiota mediates experimental AKI. The precise microbial populations involved and the underlying mechanisms are currently being explored. In this mini-review based on the NIH AKI O’Brien Center symposium of February 2020, we discuss data on gut microbiota in AKI with a focus on the immune system and short-chain fatty acids as mediators of microbiome-kidney crosstalk.

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IKK1 aggravates ischemia–reperfusion kidney injury by promoting the differentiation of effector T cells

Song

Paust

et al. 2023

Cell. Mol. Life Sci.

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Ischemia–reperfusion injury (IRI) is one of the major causes of acute kidney injury (AKI), and experimental work has revealed detailed insight into the inflammatory response in the kidney. T cells and NFκB pathway play an important role in IRI. Therefore, we examined the regulatory role and mechanisms of IkappaB kinase 1 (IKK1) in CD4+T lymphocytes in an experimental model of IRI. IRI was induced in CD4cre and CD4IKK1Δ mice. Compared to control mice, conditional deficiency of IKK1 in CD4+T lymphocyte significantly decreased serum creatinine, blood urea nitrogen (BUN) level, and renal tubular injury score. Mechanistically, lack in IKK1 in CD4+T lymphocytes reduced the ability of CD4 lymphocytes to differentiate into Th1/Th17 cells. Similar to IKK1 gene ablation, pharmacological inhibition of IKK also protected mice from IRI. Together, lymphocyte IKK1 plays a pivotal role in IRI by promoting T cells differentiation into Th1/Th17 and targeting lymphocyte IKK1 may be a novel therapeutic strategy for IRI.

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T Lymphocytes in Acute Kidney Injury and Repair

Cited by 34 publications

References 60 publications

Large animal models for translational research in acute kidney injury

Large animal models for translational research in acute kidney injury

Gut Microbiome and AKI: Roles of the Immune System and Short-Chain Fatty Acids

IKK1 aggravates ischemia–reperfusion kidney injury by promoting the differentiation of effector T cells

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