Tgfb1‐mediated Regulation of Microglia Maturation and Activation

Abstract

The pleiotropic cytokine transforming growth factor‐beta 1 (TGFβ1) has been shown to play pivotal roles in a variety of different cell types including immune cells such as T cells, monocytes/macrophages as well as microglia. As the resident immune cell population of the central nervous system (CNS), microglia are essential effector cells during physiological and pathological events. Microglia originate from mesodermal progenitors that arise from the yolk sac and colonize the embryonic CNS where they adopt a mature microglia‐specific phenotypic pattern including expression of P2ry12, Tmem119, Olfml3, Siglech, Gpr34, Hexb, and Fcrls. The differentiation and maturation of postnatal microglia, as well as the regulation of the complex functional repertoire of mature microglia, needs to be carefully orchestrated. Here, we demonstrate that the deletion of Tgfbr2 in early postnatal microglia results in a loss of microglia maturation whereas silencing of TGFβ signaling in adult microglia does neither result in impairment of the microglia‐specific gene expression signatures, nor is microglial survival and maintenance affected. Tgfbr2‐deficient microglia were characterized by distinct morphological changes and transcriptome analysis using RNAseq revealed that loss of TGFβ signaling results in the upregulation of microglia activation and priming markers. Taken together, recent studies employing sophisticated transgenic approaches to silence microglial TGFβ signaling have revealed that TGFβ1 is indispensable for microglia maturation and the establishment of the microglia‐specific gene expression pattern as well as the homeostasis of adult microglia and the control of excessive microglia activation.