AUTHOR=Neidert Nicolas , von Ehr Alexander , Zöller Tanja , Spittau Björn 

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

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.01728

DOI=10.3389/fimmu.2018.01728

ISSN=1664-3224

ABSTRACT=<p>Microglia maturation takes place during the postnatal weeks and is characterized by the establishment of a unique microglia-specific gene expression pattern. <italic>Tmem119, Fcrls, Hexb</italic>, and <italic>Olfml3</italic> 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 <italic>Olfml3</italic> expression in adult microglia and further provide evidence that TGFβ1 induces upregulation of <italic>Olfml3</italic> expression in postnatal microglia. Using chromatin immunoprecipitation and microglia-specific silencing of TGFβ signaling <italic>in vitro</italic> and <italic>in vivo</italic>, 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.</p>