Silencing of TGFβ signalling in microglia results in impaired homeostasis

Tanja Zöller, Artur Schneider, Christian Kleimeyer, Takahiro Masuda, Phani Sankar Potru, Dietmar Pfeifer, Thomas Blank, Marco Prinz, Björn Spittau

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

TGFβ1 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 neurodegenerative diseases and, thus, underlie stringent control by endogenous regulatory factors including TGFβ1. 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 TGFβ 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 TGFβ signalling to regulate microglia adaptive changes.

Original languageEnglish
Article number4011
JournalNature communications
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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  • Cite this

    Zöller, T., Schneider, A., Kleimeyer, C., Masuda, T., Potru, P. S., Pfeifer, D., Blank, T., Prinz, M., & Spittau, B. (2018). Silencing of TGFβ signalling in microglia results in impaired homeostasis. Nature communications, 9(1), [4011]. https://doi.org/10.1038/s41467-018-06224-y