Transcriptomics,Genomics

Dataset Information

159

Opposite functions of microglial and macrophagial TNFR2 in EAE pathogenesis: the good versus the bad.


ABSTRACT: In MS pathophysiology, soluble tumor necrosis factor (TNF) has been attributed detrimental functions, whereas transmembrane TNF promotes neurorepair primarily by activating TNF receptor 2 (TNFR2). Here we investigate the role of TNFR2 in microglia and peripheral monocyte/macrophages in EAE using novel cell-specific conditional knockouts. We show that microglial TNFR2 ablation leads to early onset of EAE, with increased CNS leucocyte infiltration, T cell activation, and demyelination. TNFR2-ablated microglia shows a more pro-inflammatory phenotype, with dysregulation of genes controlling innate immunity and host defense. Conversely, monocyte/macrophagial TNFR2 ablation results in EAE suppression, with impaired peripheral T cell activation. Our work uncovers a dichotomy of function for TNFR2 in myeloid cells, with microglial TNFR2 providing protective signals to contain disease, and monocyte/macrophagial TNFR2 driving immune activation and EAE initiation. This needs to be taken into account when targeting TNFR2 for therapeutic purposes in neuroinflammatory diseases to which both populations are key contributors. Overall design: RNA-seq of microglia from TNFR2 KO mice and control mice at onset of EAE.

INSTRUMENT(S): Illumina HiSeq 2500 (Mus musculus)

SUBMITTER: Han Gao  

PROVIDER: GSE78082 | GEO | 2016-11-21

SECONDARY ACCESSION(S): PRJNA312582

REPOSITORIES: GEO

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