Silencing of TGFβ signalling in microglia results in impaired homeostasis

TGF beta 1 has been implicated in regulating functional aspects of several distinct immune cell populations including central nervous system (CNS) resident microglia. Activation and priming of microglia have been demonstrated to contribute to the progression of neurode-generative diseases and, thus, underlie stringent control by endogenous regulatory factors including TGF beta 1. Here, we demonstrate that deletion of Tgfbr2 in adult postnatal microglia does neither result in impairment of the microglia-specific gene expression signatures, nor is microglial survival and maintenance affected. Tgfbr2-deficient microglia were characterised by distinct morphological changes and transcriptome analysis using RNAseq revealed that loss of TGF beta signalling results in upregulation of microglia activation and priming markers. Moreover, protein arrays demonstrated increased secretion of CXCL10 and CCL2 accompanied by activation of immune cell signalling as evidenced by increased phosphorylation of TAK1. Together, these data underline the importance of microglial TGF beta signalling to regulate microglia adaptive changes.