Opposing Functions of Microglial and Macrophagic TNFR2 in the Pathogenesis of Experimental Autoimmune Encephalomyelitis

Han Gao, Matt C. Danzi, Claire S. Choi, Mehran Taherian, Camilla Dalby-Hansen, Ditte G. Ellman, Pernille M. Madsen, John Bixby, Vance Lemmon, Kate L. Lambertsen, Roberta Brambilla

Research output: Contribution to journalArticle

41 Scopus citations


In multiple sclerosis (MS), soluble tumor necrosis factor (TNF) is detrimental via activation of TNF receptor 1 (TNFR1), whereas transmembrane TNF is beneficial primarily by activating TNF receptor 2 (TNFR2). Here, we investigate the role of TNFR2 in microglia and monocytes/macrophages in experimental autoimmune encephalomyelitis (EAE), a model of MS, by cell-specific gene targeting. We show that TNFR2 ablation in microglia leads to early onset of EAE with increased leukocyte infiltration, T cell activation, and demyelination in the central nervous system (CNS). Conversely, TNFR2 ablation in monocytes/macrophages results in EAE suppression with impaired peripheral T cell activation and reduced CNS T cell infiltration and demyelination. Our work uncovers a dichotomy of function for TNFR2 in myeloid cells, with microglial TNFR2 providing protective signals to contain disease and monocyte/macrophagic TNFR2 driving immune activation and EAE initiation. This must be taken into account when targeting TNFR2 for therapeutic purposes in neuroinflammatory diseases.

Original languageEnglish (US)
Pages (from-to)198-212
Number of pages15
JournalCell Reports
Issue number1
StatePublished - Jan 3 2017



  • cytokines
  • macrophages
  • microglia
  • multiple sclerosis
  • neuroinflammation
  • TNF signaling
  • tumor necrosis factor

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Gao, H., Danzi, M. C., Choi, C. S., Taherian, M., Dalby-Hansen, C., Ellman, D. G., Madsen, P. M., Bixby, J., Lemmon, V., Lambertsen, K. L., & Brambilla, R. (2017). Opposing Functions of Microglial and Macrophagic TNFR2 in the Pathogenesis of Experimental Autoimmune Encephalomyelitis. Cell Reports, 18(1), 198-212. https://doi.org/10.1016/j.celrep.2016.11.083