IKK1 aggravates ischemia-reperfusion kidney injury by promoting the differentiation of effector T cells.
Ning SongYang XuHans-Joachim PaustUlf PanzerMaria Mercedes de Las NoriegaLinlin GuoThomas RennéJiabin HuangXianglin MengMingyan ZhaoFriedrich ThaissPublished in: Cellular and molecular life sciences : CMLS (2023)
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.
Keyphrases
- acute kidney injury
- inflammatory response
- ischemia reperfusion injury
- peripheral blood
- oxidative stress
- nk cells
- cardiac surgery
- induced apoptosis
- metabolic syndrome
- gene expression
- dendritic cells
- single cell
- cell death
- atrial fibrillation
- lps induced
- smoking cessation
- nuclear factor
- cell cycle arrest
- insulin resistance