Astrocyte-restricted ablation of interleukin-17-induced Act1-mediated signaling ameliorates autoimmune encephalomyelitis

Immunity. 2010 Mar 26;32(3):414-25. doi: 10.1016/j.immuni.2010.03.004. Epub 2010 Mar 18.


Interleukin-17 (IL-17) secreted by T helper 17 (Th17) cells is essential in the development of experimental autoimmune encephalomyelitis (EAE). However, it remains unclear how IL-17-mediated signaling in different cellular compartments participates in the central nervous system (CNS) inflammatory process. We examined CNS inflammation in mice with specific deletion of Act1, a critical component required for IL-17 signaling, in endothelial cells, macrophages and microglia, and neuroectoderm (neurons, astrocytes, and oligodendrocytes). In Act1-deficient mice, Th17 cells showed normal infiltration into the CNS but failed to recruit lymphocytes, neutrophils, and macrophages. Act1 deficiency in endothelial cells or in macrophages and microglia did not substantially impact the development of EAE. However, targeted Act1 deficiency in neuroectoderm-derived CNS-resident cells resulted in markedly reduced severity in EAE. Specifically, Act1-deficient astrocytes showed impaired IL-17-mediated inflammatory gene induction. Thus, astroctyes are critical in IL-17-Act1-mediated leukocyte recruitment during autoimmune-induced inflammation of the CNS.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / deficiency
  • Adaptor Proteins, Signal Transducing / immunology*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Astrocytes / immunology*
  • Astrocytes / metabolism
  • Cell Survival
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Gene Expression Regulation
  • Interleukin-17 / immunology*
  • Macrophages / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Signal Transduction*
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology


  • Adaptor Proteins, Signal Transducing
  • Interleukin-17
  • Traf3ip2 protein, mouse