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Culturing Microglia from the Neonatal and Adult Central Nervous System
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Silencing of TGFβ signalling in microglia results in impaired homeostasis

Tanja Zöller1,2, Artur Schneider1, Christian Kleimeyer1

  • 1Institute for Anatomy and Cell Biology, Department of Molecular Embryology, Faculty of Medicine, University of Freiburg, 79104, Freiburg, Germany.

Nature Communications
|October 3, 2018
PubMed

Insights

Deleting Tgfbr2 in adult microglia did not affect their survival or gene expression. However, it led to distinct morphological changes and increased activation markers, highlighting TGFβ1 signaling

Area of Science:

  • Neuroimmunology
  • Cellular and Molecular Neuroscience
  • Microglia Biology

Background:

  • Transforming growth factor beta 1 (TGFβ1) regulates immune cells, including microglia in the central nervous system (CNS).
  • Microglial activation and priming are implicated in neurodegenerative disease progression.
  • Endogenous factors like TGFβ1 are crucial for controlling microglial responses.

Purpose of the Study:

  • To investigate the role of TGFβ receptor 2 (Tgfbr2) in adult postnatal microglia.
  • To determine the impact of Tgfbr2 deletion on microglial gene expression, survival, and activation states.

Main Methods:

  • Conditional deletion of Tgfbr2 in adult microglia.
  • RNA sequencing (RNAseq) for transcriptome analysis.
  • Protein arrays to assess cytokine secretion and signaling pathway activation.

Main Results:

  • Tgfbr2 deletion in microglia did not impair microglia-specific gene expression, survival, or maintenance.
  • Tgfbr2-deficient microglia exhibited altered morphology.
  • Transcriptome analysis revealed upregulation of microglia activation and priming markers.
  • Increased secretion of CXCL10 and CCL2 was observed, along with enhanced immune cell signaling (e.g., TAK1 phosphorylation).

Conclusions:

  • Microglial TGFβ signaling is essential for regulating adaptive changes in microglia.
  • Loss of Tgfbr2 leads to a more activated microglial phenotype.
  • These findings underscore the importance of TGFβ signaling in maintaining microglial homeostasis and response modulation within the CNS.

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