ORIGINAL RESEARCH published: 31 March 2020 doi: 10.3389/fncel.2020.00066 Edited by: Kyoungho Suk, Kyungpook National University, South Korea Reviewed by: Jiawei Zhou, Institute of Neuroscience (CAS), China Akira Monji, Saga University, Japan Rommy Von Bernhardi, Pontifical Catholic University of Chile, Chile *Correspondence: Björn Spittau bjoern.spittau@med.uni-rostock.de Specialty section: This article was submitted to Non-Neuronal Cells, a section of the journal Frontiers in Cellular Neuroscience Received: 27 November 2019 Accepted: 04 March 2020 Published: 31 March 2020 Citation: von Ehr A, Attaai A, Neidert N, Potru PS, Ruß T, Zöller T and Spittau B (2020) Inhibition of Microglial TGFβ Signaling Increases Expression of Mrc1. Front. Cell. Neurosci. 14:66. doi: 10.3389/fncel.2020.00066 Inhibition of Microglial TGFβ Signaling Increases Expression of Mrc1 Alexander von Ehr 1 , Abdelraheim Attaai 1,2 , Nicolas Neidert 1 , Phani Sankar Potru 3 , Tamara Ruß 3 , Tanja Zöller 3 and Björn Spittau 3,4 * 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 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 CreERT 2 :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: microglia, Mrc1, CD206, TGFβ1, TGFβ signaling INTRODUCTION The central nervous system (CNS) is colonized by primitive macrophage precursors from the yolk sac (Ginhoux et al., 2010) during mid- and late-embryonic development, which further give rise to adult microglia involving PU.1- as well as IRF8-dependent signaling pathways (Kierdorf et al., 2013). The CSFR1/IL-34 receptor/ligand pair controls the homing of microglia toward the CNS parenchyma (Ginhoux et al., 2010; Greter et al., 2012), and perinatal microglia maturation is characterized by the establishment of a microglia-specific gene expression pattern involving genes such as Olfml3, Tmem119, Hexb, Fcrls, Tgfbr1, P2ry12, and Gpr34, which allows a clear discrimination between the microglia and the other macrophage populations (Gautier et al., 2012; Beutner et al., 2013; Chiu et al., 2013; Hickman et al., 2013). This molecular signature is dependent Frontiers in Cellular Neuroscience | www.frontiersin.org 1 March 2020 | Volume 14 | Article 66