Inhibition of Microglial TGFβ Signaling Increases Expression of Mrc1

Alexander von Ehr; Abdelraheim Attaai; Nicolas Neidert; Phani Sankar Potru; Tamara Ruß; Tanja Zöller; Björn Spittau

doi:10.3389/fncel.2020.00066

Inhibition of Microglial TGFβ Signaling Increases Expression of Mrc1

Front Cell Neurosci. 2020 Mar 31:14:66. doi: 10.3389/fncel.2020.00066. eCollection 2020.

Authors

Alexander von Ehr¹, Abdelraheim Attaai^{1

2}, Nicolas Neidert¹, Phani Sankar Potru³, Tamara Ruß³, Tanja Zöller³, Björn Spittau^{3

4}

Affiliations

¹ Department of Molecular Embryology, Faculty of Medicine, Institute for Anatomy and Cell Biology, University of Freiburg, Freiburg, Germany.
² Department of Anatomy and Histology, Faculty of Veterinary Medicine, Assiut University, Assiut, Egypt.
³ Institute of Anatomy, University of Rostock, Rostock, Germany.
⁴ Centre for Translational Neurosciences Rostock, Rostock, Germany.

Abstract

Microglia are constantly surveying their microenvironment and rapidly react to impairments by changing their morphology, migrating toward stimuli and adopting gene expression profiles characterizing their activated state. The increased expression of the M2-like marker Mannose receptor 1 (Mrc1), which is also referred to as CD206, in microglia has been reported after M2-like activation in vitro and in vivo. Mrc1 is a 175-kDa transmembrane pattern recognition receptor which binds a variety of carbohydrates and is involved in the pinocytosis and the phagocytosis of immune cells, including microglia, and thought to contribute to a neuroprotective microglial phenotype. Here we analyzed the effects of TGFβ signaling on Mrc1 expression in microglia in vivo and in vitro. Using C57BL/6 wild type and Cx3cr1 ^CreERT2 :R26-YFP:Tgfbr2 ^fl/fl mice-derived microglia, we show that the silencing of TGFβ signaling results in the upregulation of Mrc1, whereas recombinant TGFβ1 induced the delayed downregulation of Mrc1. Furthermore, chromatin immunoprecipitation experiments provided evidence that Mrc1 is not a direct Smad2/Smad4 target gene in microglia. Altogether our data indicate that the changes in Mrc1 expression after the activation or the silencing of microglial TGFβ signaling are likely to be mediated by modifications of the secondary intracellular signaling events influenced by TGFβ signaling.

Keywords: CD206; Mrc1; TGFβ signaling; TGFβ1; microglia.