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.
Highlights
Hundred years ago, Pío del Río-Hortega described microglia as the resident immune cells of the central nervous system (CNS) and already proposed a mesodermal origin of these cells in a collection of original papers, which have been made available in translated English versions [1]
We provide evidence that Olfactomedin-like 3 (Olfml3) is a direct Transforming growth factor β1 (TGFβ1)/Smad2 target gene and further revealed that postnatal microglial TGFβ signaling is essential for Olfml3 upregulation whereas lack of TGFβ1 signal transduction is dispensable for the maintenance of microglial Olfml3 expression in vivo
We have recently demonstrated that microglial TGFβ signaling is activated at postnatal day 7 (P7) and, precedes the establishment of the microglial gene expression pattern [10]
Summary
Pío del Río-Hortega described microglia as the resident immune cells of the central nervous system (CNS) and already proposed a mesodermal origin of these cells in a collection of original papers, which have been made available in translated English versions [1]. To the unique and distinct origin, microglia further adopt a cell type-specific gene expression pattern including Olfactomedin-like 3 (Olfml3), which discriminates these CNS immune cells from other macrophage populations [5,6,7,8]. The development of this microglia-specific molecular signature occurs during the first postnatal weeks in mice and includes the induction of genes such as Tmem119, Hexb, Fcrls, and Tgfbr1 [9, 10]. It is of utmost interest to understand which endogenous factors are involved in the
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