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Updated: Jul 1, 2025

Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
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Development and Functional Characterization of Murine Tolerogenic Dendritic Cells

Published on: May 18, 2018

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Matrix metalloproteinase-8 regulates dendritic cell tolerance in late polymicrobial sepsis via the nuclear factor

Zhong-Qiu Lu1, Chen Zhang1, Lin-Jun Zhao1,2

  • 1Department of Emergency Medicine, The First Affiliated Hospital of Wenzhou Medical University, Fanhai West Road, Ouhai District, Wenzhou 325000, China.

Burns & Trauma
|March 1, 2024
PubMed
Abstract

Insights

Matrix metalloproteinase-8 (MMP8) drives sepsis-induced immune tolerance in dendritic cells (DCs). Reducing MMP8 protects against sepsis lethality and organ dysfunction by restoring immune responses.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Tolerogenic dendritic cells (DCs) are linked to poor sepsis prognosis.
  • Matrix metalloproteinases (MMPs) possess immunomodulatory functions, but their role in DC reprogramming during sepsis is unclear.

Purpose of the Study:

  • To investigate the role of MMPs in sepsis-induced DC tolerance.
  • To elucidate the mechanisms by which MMPs contribute to DC functional reprogramming in sepsis.

Main Methods:

  • Cecal ligation and puncture (CLP) model in mice to induce late sepsis.
  • Microarray analysis to detect MMP family expression in sepsis-induced tolerogenic DCs.
  • In vitro and in vivo assessments of MMP8's role in DC differentiation, maturation, and reprogramming.

Main Results:

  • Sepsis-induced DCs showed elevated levels of MMP8, MMP9, MMP14, MMP19, MMP25, and MMP27, with MMP8 being the most prominent.
  • MMP8 deficiency ameliorated sepsis-induced DC immune tolerance both in vivo and in vitro.
  • Adoptive transfer of MMP8-knockdown DCs improved sepsis survival, reduced organ dysfunction, suppressed regulatory T cells, and enhanced Th1 responses.

Conclusions:

  • Elevated MMP8 in septic DCs may act as a negative feedback mechanism.
  • This feedback loop suppresses proinflammatory responses and induces DC tolerance during sepsis.
  • MMP8's effect on DC tolerance is linked to the nuclear factor kappa-B p65/β-catenin pathway.
Keywords:
Dendritic cellsImmune toleranceMatrix metalloproteinasesNuclear factor kappa-BSepsisSignaling pathwayβ-catenin

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