Myeloid-derived suppressor cells alleviate renal ischemia-reperfusion injury in mice by inhibiting inflammatory response

doi:10.3877/cma.j.issn.1674-3903.2023.01.006

Abstract

Abstract:

Objective

To investigate the effect and mechanism of myeloid-derived suppressor cells (MDSCs) on renal ischemia-reperfusion injury (IRI) in mice.

Methods

A total of 15 male C57BL/6 mice were randomly divided into Sham group (n=5), IRI group (n=5), IRI combined with MDSCs transfusion group (IRI+ MDSC group, n=5). Twenty-four hours after perfusion, blood and kidney tissue samples of mice were collected, and the pathological changes of kidney tissue were observed by hematoxylin-eosin (HE) staining, and the contents of blood urea nitrogen (BUN) and serum creatinine (Cr) were detected. Serum levels of cytokines TNF-α, IFN-γ, IL-6 and IL-10 were detected by ELISA. T-cell activation in spleen was detected by flow cytometry. One-way ANOVA was used to compare the differences between multiple groups.

Results

Compared with the IRI group, the IRI+ MDSC group showed significantly improved renal function [Cr: (105±13) and (176±20) μmol/L, BUN: (34.1±1.4) and (29.6±3.1) mmol/L, P<0.05]. The necrosis degree and range of renal tubular epithelial cells and inflammatory cell infiltration degree were reduced in the IRI+ MDSC group. Paller scores were better in the IRI+ MDSC group than those in the IRI group [(55.0±3.0) vs. (40.6±6.7), P<0.05]. Serum levels of pro-inflammatory cytokines [TNF-α: (452±55) vs. (605±73) pg/mL, IFN-γ: (405±101) vs. (576±76) pg/mL, and IL-6: (459±37) vs. (863±20) pg/mL] in the IRI+ MDSC group were lower than those in IRI group (all P<0.05), respectively. However, the level of anti-inflammatory cytokine IL-10 was higher in the IRI+ MDSC group [(1519±244) pg/mL]. At the same time, the levels of activated CD4⁺ T cells and CD8⁺ T cells in spleen of the IRI+ MDSC group were lower than those of the IRI group, which were (15.6±1.3)% and (20.2±1.4)%, (31.8±1.8)% and (40.4±2.0)%, respectively, and the differences were statistically significant (all P<0.05).

Conclusion

MDSCs induced in vitro can alleviate renal injury by inhibiting the inflammatory response after IRI.

Key words: Myeloid-derived suppressor cell, Ischemia-reperfusion injury, Renal, Inflammatory response, Mice

Xingzhe Zhang, Bingxuan Zheng, Ge Deng, Meng Dou, Yuting Shi, Tian Wei, Yingcong Guo, Feng Han, Yanlong Zhao, Chenguang Ding, Puxun Tian. Myeloid-derived suppressor cells alleviate renal ischemia-reperfusion injury in mice by inhibiting inflammatory response[J]. Chinese Journal of Transplantation(Electronic Edition), 2023, 17(01): 42-46.

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URL: https://zhyzzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-3903.2023.01.006

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References 20

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组别	只数	肾功能		细胞因子(pg/mL)				T细胞活化(%)
组别	只数	BUN(mmol/L)	Cr(μmol/L)	TNF-α	IFN-γ	IL-6	IL-10	CD4^＋CD44^＋CD62L^－	CD8^＋CD44^＋CD62L^－
假手术组	5	15.8±1.8	27±6	86±23	104±18	96±29	114±8	13.0±2.2	21.6±2.2
IRI组	5	34.1±1.4^a	176±20^a	605±73^a	576±76^a	863±20^a	926±66^a	20.2±1.4^a	40.4±2.0^a
IRI＋MDSC组	5	29.6±3.1^a，b	105±13^a，b	452±55^a，b	405±101^a，b	459±37^a，b	1 519±244^a，b	15.6±1.3^a，b	31.8±1.8^a，b

组别	只数	肾功能		细胞因子(pg/mL)				T细胞活化(%)
组别	只数	BUN(mmol/L)	Cr(μmol/L)	TNF-α	IFN-γ	IL-6	IL-10	CD4^＋CD44^＋CD62L^－	CD8^＋CD44^＋CD62L^－
假手术组	5	15.8±1.8	27±6	86±23	104±18	96±29	114±8	13.0±2.2	21.6±2.2
IRI组	5	34.1±1.4^a	176±20^a	605±73^a	576±76^a	863±20^a	926±66^a	20.2±1.4^a	40.4±2.0^a
IRI＋MDSC组	5	29.6±3.1^a，b	105±13^a，b	452±55^a，b	405±101^a，b	459±37^a，b	1 519±244^a，b	15.6±1.3^a，b	31.8±1.8^a，b

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