Microglia-Specific Expression of Olfml3 Is Directly Regulated by Transforming Growth Factor β1-Induced Smad2 Signaling

Front Immunol. 2018 Jul 26:9:1728. doi: 10.3389/fimmu.2018.01728. eCollection 2018.

Abstract

Microglia maturation takes place during the postnatal weeks and is characterized by the establishment of a unique microglia-specific gene expression pattern. Tmem119, Fcrls, Hexb, and Olfml3 have been identified among these microglia-specific genes. Transforming growth factor β1 (TGFβ1) has been reported as a critical factor for microglia maturation and maintenance and active TGFβ signaling precedes the inductions of microglial gene expression. In this study, we demonstrate Olfml3 expression in adult microglia and further provide evidence that TGFβ1 induces upregulation of Olfml3 expression in postnatal microglia. Using chromatin immunoprecipitation and microglia-specific silencing of TGFβ signaling in vitro and in vivo, we in clearly show that Olfml3 is a direct TGFβ1/Smad2 target gene. Together, our data underline the importance of TGFβ1 as a critical regulator of microglia functions and microglia maturation and further broaden our understanding of TGFβ1-mediated effects on the resident immune cells of the central nervous system.

Keywords: Olfml3; Smad2; Smad4; microglia; transforming growth factor β1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Gene Expression Regulation*
  • Mice
  • Microglia / metabolism*
  • Organ Specificity
  • Protein Binding
  • Protein Transport
  • Signal Transduction*
  • Smad2 Protein / metabolism*
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • Smad2 Protein
  • Transforming Growth Factor beta1