Harnessing Endogenous T-Regulatory Cells in Acute Kidney Injury.
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ABSTRACT:
SUBMITTER: Sharma R
PROVIDER: S-EPMC7708413 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
Acute kidney injury (AKI) affects 20-50% of hospitalized and intensive care patients, with a sizable proportion progressing to ESRD or death (https://www.kidney.org/atoz/content/AcuteKidneyInjury). Since inflammation contributes to the pathogenesis of AKI, studies on T-regulatory cells (Tregs), which suppress inflammation are important. Here, we highlight advances that utilize Tregs for intervention in AKI and were presented at the 25th International Conference on Advances in Critical Care Nephr ...[more]
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Project description:Foxp3-expressing CD4+ regulatory T cells (Tregs) make up one subset of the helper T cells (Th) and are one of the major mechanisms of peripheral tolerance. Tregs prevent abnormal activation of the immune system throughout the lifespan, thus protecting from autoimmune and inflammatory diseases. Recent studies have elucidated the role of Tregs beyond autoimmunity. Tregs play important functions in controlling not only innate and adaptive immune cell activation, but also regulate nonimmune cell function during insults and injury. Inflammation contributes to a multitude of acute and chronic diseases affecting the kidneys. This review examines the role of Tregs in pathogenesis of renal inflammatory diseases and explores the approaches for enhancing Tregs for prevention and therapy of renal inflammation.
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Project description:Sepsis is the primary cause of acute kidney injury (AKI) and is associated with high mortality rates. Growing evidence suggests that noncoding RNAs are vitally involved in kidney illnesses, whereas the role of circular RNAs (circRNAs) in sepsis-induced AKI (SAKI) remains largely unknown. In this present study, caecal ligation and puncture (CLP) in mice was performed to establish an SAKI model. The expression of circRNAs and mRNAs was analysed using circRNA microarray or next-generation sequencing. The results revealed that the expressions of 197 circRNAs and 2509 mRNAs were dysregulated. Validation of the selected circRNAs was performed by qRT-PCR. Bioinformatics analyses and chromatin immunoprecipitation demonstrated that NF-κB/p65 signalling induced the upregulation of circC3, circZbtb16, and circFkbp5 and their linear counterparts by p65 transcription in mouse tubular epithelial cells (mTECs). Furthermore, competitive endogenous RNA (ceRNA) networks demonstrated that some components of NF-κB signalling were potential targets of these dysregulated circRNAs. Among them, Tnf-α was increased by circFkbp5 through the downregulation of miR-760-3p in lipopolysaccharide (LPS)-stimulated mTECs. Knocking down circFkbp5 inhibited the p65 phosphorylation and apoptosis in injured mTECs. These findings suggest that the selected circRNAs and the related ceRNA networks provide new knowledge into the fundamental mechanism of SAKI and circFkbp5/miR-760-3p/Tnf-α axis might be therapeutic targets.
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Project description:Purpose of reviewRecent advances in T cell biology have shed light on the role of T cell subsets in the pathogenesis of acute kidney injury (AKI). The purpose of this review is to harness our understanding of recent advances in T cell biology in tissue injury and repair and provide a mechanistic insight into the role of T cells in the inflammation of AKI.Recent findingsNew specific reagents and genetic animal models have led to advances in our understanding of the role of T cell subsets involved in renal injury. Whereas some T cells promote innate renal inflammation and injury, other T cells promote protection and repair. Recent studies illuminated the pathogenic mechanisms of invariant natural killer T (NKT) cells and T helper1-type responses, and the beneficial functions of regulatory T cells and NKT cells are just beginning to be explored. Pharmacologic and cell-based therapies that influence T cell responses to experimental AKI suggest that this is a promising approach to preserve renal function.SummaryThe recent insights gained into how T cells modulate renal injury suggest that strategies targeting specific types of T cells, to either inhibit or enhance their activity, may ameliorate renal injury in patients.
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