IKK1 aggravates ischemia-reperfusion kidney injury by promoting the differentiation of effector T cells
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.
Open Access funding enabled and organized by Projekt DEAL.
DFG TH 343/12-1
National Natural Scientific Foundation of China 82172164
Heilongjiang Province Key R&D program JD22C005.
China Scholarship Council
Associated research data filesAll raw data are available via the Sequence Read Archive via GEO (GSE217696).
CommentsThe original article is available at https://link.springer.com/
Published CitationSong N, et al. IKK1 aggravates ischemia-reperfusion kidney injury by promoting the differentiation of effector T cells. Cell Mol Life Sci. 2023;80(5):125.
Publication Date19 April 2023
- Irish Centre for Vascular Biology
- School of Pharmacy and Biomolecular Sciences
- Published Version (Version of Record)