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Tenascin C regulates multiple microglial functions involving TLR4 signaling and HDAC1

Verena Haage1, Nirmeen Elmadany1, Lars Roll2

  • 1Cellular Neurosciences, Max-Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin 13125, Germany.

Brain, Behavior, and Immunity
|July 5, 2019
PubMed

Insights

Tenascin C (Tnc) regulates microglia function in early development. It impacts phagocytosis, cytokine release, and migration, partly through Toll-like receptor 4 (TLR4) and histone deacetylase 1 (HDAC1).

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Tenascin C (Tnc) is an extracellular matrix glycoprotein involved in CNS development, inflammation, fibrosis, and cancer.
  • Toll-like receptor 4 (TLR4) is highly expressed in microglia, but Tnc's effect on these cells is unknown.

Purpose of the Study:

  • To investigate the role of Tenascin C (Tnc) in regulating microglial function during early postnatal development.
  • To elucidate the involvement of Toll-like receptor 4 (TLR4) and histone deacetylase 1 (HDAC1) in Tnc-mediated microglial responses.

Main Methods:

  • Primary microglia culture and analysis of phagocytic activity, cytokine/chemokine production, and chemotaxis.
  • Assessment of Tnc's effect on microglial TLR4 expression and signaling.
  • Investigation of Tnc-induced histone deacetylase 1 (HDAC1) expression and the impact of HDAC1 inhibition.
  • Analysis of microglia from Tnc-deficient mice (Tnc-/-).

Main Results:

  • Tenascin C (Tnc) regulates microglial phagocytosis at postnatal day 4 (P4), partially dependent on microglial TLR4.
  • Tnc modulates proinflammatory cytokine/chemokine production, chemotaxis, and phagocytosis in a TLR4-dependent manner.
  • Tnc induces HDAC1 expression in microglia; HDAC1 inhibition reduces Tnc-induced IL-6 and TNF-α production.
  • Cortical microglia from Tnc-/- mice exhibit reduced HDAC1 expression at P4.

Conclusions:

  • Tenascin C (Tnc) acts as a significant regulator of microglial function during early postnatal development.
  • Tnc influences microglial phagocytosis, inflammatory responses, and migration via TLR4 and HDAC1 pathways.
  • These findings highlight Tnc's crucial role in shaping the developing central nervous system immune environment.
Keywords:
ECM protein Tenascin CEarly postnatal developmentHDAC1MicrogliaPhagocytosisTLR4

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