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IKK1 aggravates ischemia–reperfusion kidney injury by promoting the differentiation of effector T cells

Authors
  • Song, Ning
  • Xu, Yang
  • Paust, Hans-Joachim
  • Panzer, Ulf
  • de las Noriega, Maria Mercedes
  • Guo, Linlin
  • Renné, Thomas
  • Huang, Jiabin
  • Meng, Xianglin
  • Zhao, Mingyan
  • Thaiss, Friedrich
Type
Published Article
Journal
Cellular and Molecular Life Sciences
Publisher
Springer-Verlag
Publication Date
Apr 19, 2023
Volume
80
Issue
5
Identifiers
DOI: 10.1007/s00018-023-04763-2
PMID: 37074502
PMCID: PMC10115737
Source
PubMed Central
Keywords
Disciplines
  • Original Article
License
Unknown

Abstract

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. Supplementary Information The online version contains supplementary material available at 10.1007/s00018-023-04763-2.

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