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Extracellular vimentin modulates human dendritic cell activation.

Mary Beth Yu1, Joshua Guerra2, Anthony Firek3

  • 1Center for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda, University School of Medicine, Loma Linda, CA, 92354, USA; Division of Biochemistry, Department of Basic Sciences, Loma Linda, University School of Medicine, Loma Linda, CA, 92354, USA.

Molecular Immunology
|November 7, 2018
PubMed
Summary
This summary is machine-generated.

Extracellular vimentin, a protein found outside cells, suppresses adaptive immunity by reducing dendritic cell (DC) pro-inflammatory cytokine release. This finding suggests vimentin

Keywords:
Cell cultureCytokineDendritic cellsHumanLipopolysaccharideVimentin

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Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Vimentin is an intermediate filament protein typically intracellular, but found extracellularly in disease states.
  • Extracellular vimentin's role in innate immunity is known, but its impact on adaptive immunity initiation is unclear.
  • Adaptive immunity initiation involves antigen-presenting cells, such as dendritic cells (DCs), priming T cells.

Purpose of the Study:

  • To investigate how extracellular vimentin modulates lipopolysaccharide (LPS)-induced activation of human dendritic cells (DCs).
  • To determine the effect of extracellular vimentin on DC cytokine secretion and T cell differentiation.

Main Methods:

  • Cytometric bead arrays were used to measure cytokine secretion from LPS-activated DCs.
  • Flow cytometry assessed surface molecule expression on DCs.
  • Co-culture experiments with DCs and naïve CD4+ T cells evaluated T cell differentiation.

Main Results:

  • Extracellular vimentin decreased LPS-induced secretion of IL-6 and IL-12 while increasing IL-10 from DCs.
  • Vimentin did not significantly alter DC surface expression of MHC I, MHC II, costimulatory molecules, or maturation markers.
  • Vimentin reduced IFN-γ secretion in T cells, suggesting reduced Th1 differentiation.

Conclusions:

  • Extracellular vimentin inhibits pro-inflammatory adaptive immune responses by modulating DC cytokine production.
  • Vimentin may suppress adaptive immunity in cancer or trauma, potentially preventing autoimmunity.
  • Extracellular vimentin represents a potential therapeutic target for inflammatory diseases.