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

被引：6

作者：

Song, Ning ^{[1
,2
]}

Xu, Yang ^{[3
]}

Paust, Hans-Joachim ^{[2
]}

Panzer, Ulf ^{[2
]}

de las Noriega, Maria Mercedes ^{[4
]}

Guo, Linlin ^{[2
]}

Renne, Thomas ^{[5
,6
,7
]}

Huang, Jiabin ^{[8
]}

Meng, Xianglin ^{[1
,9
,10
]}

Zhao, Mingyan ^{[1
,10
]}

Thaiss, Friedrich ^{[2
]}

机构：

[1] Harbin Med Univ, Affiliated Hosp 1, Dept Crit Care Med, Youzheng St 23, Harbin 150001, Peoples R China

[2] Univ Med Ctr Hamburg Eppendorf, Dept Med 3, Martinistr 52, D-20246 Hamburg, Germany

[3] Univ Med Ctr Hamburg Eppendorf, Dept Gen Visceral & Thorac Surg, D-20246 Hamburg, Germany

[4] Univ Med Ctr Hamburg Eppendorf, Dept Pathol, Renal Pathol, D-20246 Hamburg, Germany

[5] Univ Med Ctr Hamburg Eppendorf, Inst Clin Chem & Lab Med, D-20246 Hamburg, Germany

[6] Royal Coll Surgeons Ireland, Irish Ctr Vasc Biol, Sch Pharm & Biomol Sci, Dublin, Ireland

[7] Johannes Gutenberg Univ Mainz, Ctr Thrombosis & Hemostasis CTH, Med Ctr, D-55131 Mainz, Germany

[8] Univ Med Ctr Hamburg Eppendorf, Inst Med Microbiol Virol & Hyg, D-20246 Hamburg, Germany

[9] Fudan Univ, Shanghai Canc Ctr, Canc Inst, Shanghai 200032, Peoples R China

[10] Harbin Med Univ, Affiliated Hosp 1, Heilongjiang Prov Key Lab Crit Care Med, Harbin 150001, Peoples R China

来源：

CELLULAR AND MOLECULAR LIFE SCIENCES | 2023年 / 80卷 / 05期

关键词：

AKI; acute kidney injury; Non-canonical NF kappa B; IKKalpha; CD4(+)T cells; Th17; lymphocytes; NF-KAPPA-B; ISCHEMIA/REPERFUSION INJURY; IMMUNE-RESPONSES; SYSTEM; KINASE; ALPHA; BETA; PROGRESSION; ACTIVATION; INHIBITOR;

D O I：

10.1007/s00018-023-04763-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 NF?B 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 CD4IKK1? 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.

引用

页数：14

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