Kidney double positive T cells have distinct characteristics in normal and diseased kidneys.

Multiple types of T cells have been described and assigned pathophysiologic functions in the kidneys. However, the existence and functions of TCR+CD4+CD8+ (double positive; DP) T cells are understudied in normal and diseased murine and human kidneys. We studied kidney DPT cells in mice at baseline and after ischemia reperfusion (IR) and cisplatin injury.

Single cell and spatial transcriptomics analysis of kidney double negative T lymphocytes in normal and ischemic mouse kidneys.

T cells are important in the pathogenesis of acute kidney injury (AKI), and TCRCD4CD8 (double negative-DN) are T cells that have regulatory properties. However, there is limited information on DN T cells compared to traditional CD4 and CD8 cells. To elucidate the molecular signature and spatial dynamics of DN T cells during AKI, we performed single-cell RNA sequencing (scRNA-seq) on sorted murine DN, CD4, and CD8 cells combined with spatial transcriptomic profiling of normal and post AKI mouse kidneys.

T cell metabolic reprogramming in acute kidney injury and protection by glutamine blockade.

T cells play an important role in acute kidney injury (AKI). Metabolic programming of T cells regulates their function, is a rapidly emerging field, and is unknown in AKI. We induced ischemic AKI in C57BL/6J mice and collected kidneys and spleens at multiple time points.

Microbiome modulation after severe acute kidney injury accelerates functional recovery and decreases kidney fibrosis.

Targeting gut microbiota has shown promise to prevent experimental acute kidney injury (AKI). However, this has not been studied in relation to accelerating recovery and preventing fibrosis. Here, we found that modifying gut microbiota with an antibiotic administered after severe ischemic kidney injury in mice, particularly with amoxicillin, accelerated recovery.

Immune Checkpoint Molecule TIGIT Regulates Kidney T Cell Functions and Contributes to AKI.

Significance Statement: T cells mediate pathogenic and reparative processes during AKI, but the exact mechanisms regulating kidney T cell functions are unclear. This study identified upregulation of the novel immune checkpoint molecule, TIGIT, on mouse and human kidney T cells after AKI. TIGIT-expressing kidney T cells produced proinflammatory cytokines and had effector (EM) and central memory (CM) phenotypes.

T Cell Gene Editing Using CRISPR/Cas9 and Experimental Kidney Ischemia-Reperfusion Injury.

T cells play pathophysiologic roles in kidney ischemia-reperfusion injury (IRI), and the nuclear factor erythroid 2-related factor 2/kelch-like ECH-associated protein 1 (Nrf2/Keap1) pathway regulates T cell responses. We hypothesized that clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated -knockout (KO) augments Nrf2 antioxidant potential of CD4+ T cells, and that -KO CD4+ T cell immunotherapy protects from kidney IRI. CD4+ T cell -KO resulted in significant increase of Nrf2 target genes NAD(P)H quinone dehydrogenase 1, heme oxygenase 1, glutamate-cysteine ligase catalytic subunit, and glutamate-cysteine ligase modifier subunit.

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

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.