TGFβ1 attenuates microglial IL1β release through inhibition of NLRP3 inflammasome priming

Christopher Kalischer1, Phani Sankar Potru2, Nele Lehmann2

  • 1Institute of Anatomy, University of Rostock, Rostock, Germany.

Frontiers in Immunology
|January 21, 2026
PubMed
Abstract

Insights

Transforming growth factor beta 1 (TGFβ1) suppresses inflammasome activation in microglia, reducing neuroinflammation. Silencing microglial TGFβ signaling increases pro-inflammatory gene expression, highlighting TGFβ1

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia reactivity drives neurodegeneration.
  • Inflammasomes, like NLRP3, are key in microglial activation and neuroinflammation.
  • Transforming growth factor beta 1 (TGFβ1) regulates microglial function.

Purpose of the Study:

  • To investigate TGFβ1's effect on inflammasome activation in microglia.
  • To elucidate the role of microglial TGFβ signaling in neuroinflammation.

Main Methods:

  • Utilized BV2 cells and primary microglia.
  • Employed qPCR and western blotting to assess gene and protein expression.
  • Used Cx3cr1CreERT2:R26-YFP:Tgfbr2flox/flox mice to study in vivo TGFβ signaling.

Main Results:

  • TGFβ1 inhibited LPS-induced upregulation of NLRP3 inflammasome components (Nlrp3, Casp1, Il1b).
  • TGFβ1 attenuated IL1b release following nigericin stimulation by reducing inflammasome priming.
  • In vivo silencing of microglial TGFβ signaling led to increased Casp1, Il18, and Il1b expression.

Conclusions:

  • TGFβ1 acts as a potent immunoregulatory factor for microglia.
  • TGFβ1 signaling is crucial for controlling microglial reactivity and inflammasome activation.
  • Targeting TGFβ1 may offer therapeutic strategies for neurodegenerative diseases.

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