Calcium channel Orai1 promotes lymphocyte IL-17 expression and progressive kidney injury

Mehrotra, Purvi; Sturek, Michael; Neyra, Javier A.; Basile, David P.

doi:10.1172/jci126108

Cited by 43 publications

(43 citation statements)

References 46 publications

(57 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Orai1 inhibition also reduced the nuclear accumulation of nuclear factor of activated T cells and RORγT. We suggested a requirement for Orai1 in Th17 differentiation in our recent study of a rat model of kidney injury; IL-17 expression by CD4+ cells was exclusive to those cells that expressed Orai1 and was not detected in CD4+ cells that lacked expression of this channel [ 22 ].…”

Section: T Helper 17 Definition and Rolesmentioning

confidence: 97%

“…Chung et al [50] Increased prevalence of Th17 cells was found in patients with chronic allograft nephropathy. AKI Mehrotra et al [22] Increased Th17 cells and IL-17+ and Orai+ PBMCs were detected in ICU patients with AKI vs. non-AKI patients. Maravitsa et al [51] IL-17 levels were higher in septic patients that developed AKI than those that did not.…”

Section: Acute and Chronic Rejection In Renal Transplantmentioning

confidence: 99%

See 1 more Smart Citation

T helper 17 cells in the pathophysiology of acute and chronic kidney disease

Basile

Ullah

Collet

et al. 2021

Kidney Res Clin Pract

Self Cite

View full text Add to dashboard Cite

As of 2017, the global burden of chronic kidney disease (CKD) was estimated to be approximately 9.1%, indicating that CKD is a significant healthcare concern worldwide. Global age-adjusted mortality rates for patients with CKD have declined in the last 30 years, and quality of life metrics decrease as glomerular filtration rate declines [1]. In the period between1990 and 2017, there was an approximate 41% increase in the number of patients with end-stage renal disease (ESRD). Despite this, CKD patients are more likely to die due to complications such as hypertension, cardiovascular disease, anemia, and bone and mineral Both acute and chronic kidney disease have a strong underlying inflammatory component. This review focuses primarily on T helper 17 (Th17) cells as mediators of inflammation and their potential to modulate acute and chronic kidney disease. We provide updated information on factors and signaling pathways that promote Th17 cell differentiation with specific reference to kidney disease. We highlight numerous clinical studies that have investigated Th17 cells in the setting of human kidney disease and provide updated summaries from various experimental animal models of kidney disease indicating an important role for Th17 cells in renal fibrosis and hypertension. We focus on the pleiotropic effects of Th17 cells in different renal cell types as potentially relevant to the pathogenesis of kidney disease. Finally, we highlight studies that present contrasting roles for Th17 cells in kidney disease progression.

show abstract

Section: T Helper 17 Definition and Rolesmentioning

confidence: 97%

Section: Acute and Chronic Rejection In Renal Transplantmentioning

confidence: 99%

T helper 17 cells in the pathophysiology of acute and chronic kidney disease

Basile

Ullah

Collet

et al. 2021

Kidney Res Clin Pract

Self Cite

View full text Add to dashboard Cite

show abstract

“…IL-1 signaling dominates the phenomenon and its suppression pushes lymphocytes phenotypes to T H1 (27). Mehrota and colleagues demonstrated that T H17 cells expressing calcium channel Orai1 are solely responsible for IL-17 production after IRI and, ultimately, for renal injury (46). A 10-fold increase in circulating Orai1 + T H17 cells are found in ICU patients with AKI compared to those without (46).…”

Section: T H17 Cellsmentioning

confidence: 99%

“…Mehrota and colleagues demonstrated that T H17 cells expressing calcium channel Orai1 are solely responsible for IL-17 production after IRI and, ultimately, for renal injury (46). A 10-fold increase in circulating Orai1 + T H17 cells are found in ICU patients with AKI compared to those without (46). In vivo, intra-renal expression of Orai1 persisted for days after AKI resolution and its inhibition prevented the transition to chronic kidney disease (CKD) (46).…”

Section: T H17 Cellsmentioning

confidence: 99%

“…A 10-fold increase in circulating Orai1 + T H17 cells are found in ICU patients with AKI compared to those without (46). In vivo, intra-renal expression of Orai1 persisted for days after AKI resolution and its inhibition prevented the transition to chronic kidney disease (CKD) (46). Intriguingly, the kidney also possesses mechanisms to counteract T H17 cell activation.…”

Section: T H17 Cellsmentioning

confidence: 99%

See 1 more Smart Citation

T Cells and Acute Kidney Injury: A Two-Way Relationship

2020

View full text Add to dashboard Cite

Acute Kidney Injury (AKI) complicates up to 10% of hospital admissions substantially increasing patient morbidity and mortality. Experimental evidence supports that AKI initiation and maintenance results from immune-mediated damage. Exogenous injury sources directly damage renal cells which produce pro-inflammatory mediators recruiting immune cells and furthering kidney injury. Many AKI studies focus on activation of innate immunity; major components include complement pathways, neutrophils, and monocytes. Recently, growing evidence emphasizes T lymphocytes role in affecting AKI pathogenesis and magnitude. In particular, T helper 17 lymphocytes enhance tissue injury by recruiting neutrophils and other inflammatory cells, while regulatory T cells conversely reduce renal injury and facilitate repair. Intriguingly, evidence supports local parenchymal-T cell interactions as essential to producing T cell phenotypic changes affecting long-term kidney and patient survival. Herein, we review T cells effects on AKI and patient outcomes and discuss related new therapeutic approaches to improve outcomes of affected individuals.

show abstract

Liposome‐Mediated Biomimetic Delivery of PLK3 Inhibitor with NIR II‐Triggered Release Prevents Renal Ischemia‐Reperfusion Injury

Zhu

Zhang

Li³

et al. 2022

Advanced Therapeutics

View full text Add to dashboard Cite

As one of the leading causes of acute kidney injury (AKI), ischemia-reperfusion injury (IRI) results in tubular necrosis and renal inflammation. Here, from gene screening, it is found that Polo-like kinase 3 (PLK3), but not other PLKs, is highly up-regulated during mouse IRI. In vivo administration of PLK3 inhibitor alleviates IRI-induced AKI, but induces myelosuppression. Thus, a novel liposome-mediated biomimetic delivery system with 1080 nm near infrared (NIR)-triggered release to specifically and efficiently delivering the inhibitor to the kidney is developed. NIR light irradiation to kidney results in an excellent effect for reduced immune cell infiltration and renal inflammation. Mechanistically, PLK3 inhibition suppresses the degradation of hypoxia-inducible factor-1𝜶 (HIF-1𝜶) and reactive oxygen species (ROS)-mediated oxidative stress, thus protecting the renal tubular epithelial cells from cell death and preventing macrophage activation and renal inflammation. Thus, the NIR light-triggered liposome system provides an efficient candidate treatment for AKI without systemic side effect.

show abstract

Calcium channel Orai1 promotes lymphocyte IL-17 expression and progressive kidney injury

Cited by 43 publications

References 46 publications

T helper 17 cells in the pathophysiology of acute and chronic kidney disease

T helper 17 cells in the pathophysiology of acute and chronic kidney disease

T Cells and Acute Kidney Injury: A Two-Way Relationship

Liposome‐Mediated Biomimetic Delivery of PLK3 Inhibitor with NIR II‐Triggered Release Prevents Renal Ischemia‐Reperfusion Injury

Contact Info

Product

Resources

About