Matrix metalloproteinase-8 regulates dendritic cell tolerance in late polymicrobial sepsis via the nuclear factor kappa-B p65/β-catenin pathway

Zhong-qiu Lu; Chen Zhang; Lin-jun Zhao; Wei Dong; Liang Lv; Yang Lu; Xiao-Yan Chen; Jie Zhang; Xin-yong Liu; Zhong Xiao; Long-wang Chen; Yong-ming Yao; Guang-ju Zhao

doi:10.1093/burnst/tkad025

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Matrix metalloproteinase-8 regulates dendritic cell tolerance in late polymicrobial sepsis via the nuclear factor kappa-B p65/β-catenin pathway

更新时间：2024-04-19

- Matrix metalloproteinase-8 regulates dendritic cell tolerance in late polymicrobial sepsis via the nuclear factor kappa-B p65/β-catenin pathway
- Burns & Trauma Vol. 12, Issue 1, (2024)
- 作者机构：
  
  1. Department of Emergency Medicine, The First Affiliated Hospital of Wenzhou Medical University
  2. Translational Medicine Research Center, Medical Innovation Research Division and Fourth Medical of the Chinese PLA General Hospital
  3. Department of Emergency Medicine
  4. Zhejiang University School of Medicine
  5. Department of Rheumatology, Wenzhou People's Hospital
- 作者简介：
- 基金信息：
- DOI：10.1093/burnst/tkad025
  CLC：
- Published：2024，
  
  Published Online：28 February 2024，
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Zhong-qiu Lu, Chen Zhang, Lin-jun Zhao, Wei Dong, Liang Lv, Yang Lu, Xiao-Yan Chen, Jie Zhang, Xin-yong Liu, Zhong Xiao, Long-wang Chen, Yong-ming Yao, Guang-ju Zhao, Matrix metalloproteinase-8 regulates dendritic cell tolerance in late polymicrobial sepsis via the nuclear factor kappa-B p65/β-catenin pathway, Burns & Trauma, Volume 12, 2024, tkad025, https://doi.org/10.1093/burnst/tkad025
DOI：

Zhong-qiu Lu, Chen Zhang, Lin-jun Zhao, Wei Dong, Liang Lv, Yang Lu, Xiao-Yan Chen, Jie Zhang, Xin-yong Liu, Zhong Xiao, Long-wang Chen, Yong-ming Yao, Guang-ju Zhao, Matrix metalloproteinase-8 regulates dendritic cell tolerance in late polymicrobial sepsis via the nuclear factor kappa-B p65/β-catenin pathway, Burns & Trauma, Volume 12, 2024, tkad025, https://doi.org/10.1093/burnst/tkad025 DOI：

摘要

Abstract

BackgroundTolerogenic dendritic cells (DCs) are associated with poor prognosis of sepsis. Matrix metalloproteinases (MMPs) have been shown to have immunomodulatory effects. However

whether MMPs are involved in the functional reprogramming of DCs is unknown. The study aims to investigate the role of MMPs in sepsis-induced DCs tolerance and the potential mechanisms.MethodsA murine model of late sepsis was induced by cecal ligation and puncture (CLP). The expression levels of members of the MMP family were detected in sepsis-induced tolerogenic DCs by using microarray assessment. The potential roles and mechanisms underlying MMP8 in the differentiation

maturation and functional reprogramming of DCs during late sepsis were assessed both in vitro and in vivo.ResultsDCs from late septic mice expressed higher levels of MMP8

MMP9

MMP14

MMP19

MMP25 and MMP27

and MMP8 levels were the highest. MMP8 deficiency significantly alleviated sepsis-induced immune tolerance of DCs both in vivo and in vitro. Adoptive transfer of MMP8 knockdown post-septic bone marrow-derived DCs protected mice against sepsis-associated lethality and organ dysfunction

inhibited regulatory T-cell expansion and enhanced Th1 response. Furthermore

the effect of MMP8 on DC tolerance was found to be associated with the nuclear factor kappa-B p65/β-catenin pathway.ConclusionsIncreased MMP8 levels in septic DCs might serve as a negative feedback loop

thereby suppressing the proinflammatory response and inducing DC tolerance.

关键词

Keywords

SepsisDendritic cellsImmune toleranceMatrix metalloproteinasesSignaling pathwayβ-cateninNuclear factor kappa-B

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