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

    loading  Checking for direct PDF access through Ovid

Abstract

SUMMARY

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.

The specific function of RANKL expressed by T cells in the context of immune responses remains enigmatic. Takayanagi and colleagues show that RANKL on T cells regulates CCL20 expression by astrocytes and the recruitment of T cells into the central nervous system (CNS), a critical step in CNS autoimmunity.

Related Topics

    loading  Loading Related Articles