Regulatory T cells alleviate intracerebral hemorrhage-induced inflammatory injury in mice by modulating microglia M2 polarization through the IL-10/STAT3 pathway

Qiumeng LI; Wenqian ZHANG; Ying TAN; Guanjian ZHAO; Xiang ZHANG; Peng ZHANG; Yuan CHENG

doi:10.16016/j.1000-5404.201802129

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Regulatory T cells alleviate intracerebral hemorrhage-induced inflammatory injury in mice by modulating microglia M2 polarization through the IL-10/STAT3 pathway

更新时间：2026-01-09

- Regulatory T cells alleviate intracerebral hemorrhage-induced inflammatory injury in mice by modulating microglia M2 polarization through the IL-10/STAT3 pathway
- Journal of Third Military Medical University Vol. 40, Issue 16, Pages: 1461-1468(2018)
- 作者机构：
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81371674);the General Program of National Natural Science Foundation of China(81401505)
- DOI：10.16016/j.1000-5404.201802129
  CLC：
- Received：20 November 2017，
  
  Published：30 August 2018
- 稿件说明：
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Qiumeng LI, Wenqian ZHANG, Ying TAN, et al. Regulatory T cells alleviate intracerebral hemorrhage-induced inflammatory injury in mice by modulating microglia M2 polarization through the IL-10/STAT3 pathway[J]. Journal of Third Military Medical University, 2018, 40(16): 1461-1468.
DOI：

Qiumeng LI, Wenqian ZHANG, Ying TAN, et al. Regulatory T cells alleviate intracerebral hemorrhage-induced inflammatory injury in mice by modulating microglia M2 polarization through the IL-10/STAT3 pathway[J]. Journal of Third Military Medical University, 2018, 40(16): 1461-1468. DOI： 10.16016/j.1000-5404.201802129.

摘要

Abstract

Objective

To investigate the effect of regulatory T cells (Tregs) on inflammatory injury induced by intracerebral hemorrhage (ICH) and explore the molecular mechanism.

Methods

Twenty C57BL/6 mice were randomized into 4 equal groups

namely ICH with Tregs treatment group

ICH model group

sham operation group

and sham operation with Tregs treatment group.Mouse models of ICH were established by injecting non-anti-coagulated autologous blood (20 μL) into the basal ganglia

followed 24 h later by injection of autologous Tregs

via

the tail vein (normal saline was injected in ICH model and sham operation groups).The changes in neurological deficit score

brain tissue water content

and hematoma volume were observed in the mice 4 days after ICH.ELISA was used to detect the levels of interleukin-6 (IL-6)

tumor necrosis factor-α (TNF-α

) IL-10

and transforming growth factor-β (TGF-β) in the brain tissues

and PCR was used for detecting the changes in the mRNA expression of the signature genes (CCL3

iNOS

Arg1

and Ym1);immunofluorescence assay was used for detecting the specialized protein markers M1 (CD16/32) and M2 (CD206).We also established a BV2 cells/Tregs transwell co-culture system

in which the same inflammatory cytokines and mRNA expressions of the signature genes were detected; Western blotting was used to detect the protein expression of STAT3

p-STAT3 and TGF-β in the co-culture.

Results

In mice with ICH

intravenous delivery of Tregs significantly improved the neurological function

relieved cerebral edema and reduced the hematoma volume (

0.05);administration of Tregs also significantly lowered the expression levels of IL-6

TNF-α

CCL3

and iNOS and increased the levels of IL-10

F-β

Arg1

and Ym1 in the brain tissues (

0.05).In the co-culture of Tregs and BV2 cells

the expression levels of IL-6

TNF-α

CCL3

iNOS and p-STAT3 increased and those of IL-10

TGF-β

Arg1

and Ym1 decreased significantly as compared with those in the control group (

0.05).Neutralization of IL-10 in the co-culture caused significant reductions in the expression levels of p-STAT3 and TGF-β proteins and Arg1 and Ym1 mRNA (

0.05).

Conclusion

Tregs alleviate ICH-induced inflammatory injury in mice possibly by modulating microglia M2 polarization through the IL-10/STAT3 pathway.

关键词

Keywords

references

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