Inhibition of the TNF Family Cytokine RANKL Prevents Autoimmune Inflammation in the Central Nervous System

Immunity. 2015 Dec 15;43(6):1174-85. doi: 10.1016/j.immuni.2015.10.017. Epub 2015 Dec 8.


The central nervous system (CNS) is an immunologically privileged site protected from uncontrolled access of T cells by the blood-brain barrier (BBB), which is breached upon autoimmune inflammation. Here we have shown that receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL) on T cells regulates C-C type chemokine ligand 20 (CCL20) production by astrocytes and T cell localization in the CNS. Importantly, mice specifically lacking RANKL in T cells were resistant to experimental autoimmune encephalomyelitis (EAE) due to altered T cell trafficking. Pharmacological inhibition of RANKL prevented the development of EAE without affecting the peripheral immune response, indicating that RANKL is a potential therapeutic target for treating autoimmune diseases in the CNS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / immunology
  • Chemotaxis, Leukocyte / immunology*
  • Coculture Techniques
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Immunohistochemistry
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Knockout
  • RANK Ligand / deficiency
  • RANK Ligand / immunology*
  • Real-Time Polymerase Chain Reaction
  • T-Lymphocytes / immunology*


  • RANK Ligand
  • Tnfsf11 protein, mouse