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

Matteo M. Guerrini, Kazuo Okamoto, Noriko Komatsu, Shinichiro Sawa, Lynett Danks, Josef M. Penninger, Tomoki Nakashima, Hiroshi Takayanagi

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Abstract

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.

Original languageEnglish
Pages (from-to)1174-1185
Number of pages12
JournalImmunity
Volume43
Issue number6
DOIs
Publication statusPublished - Jan 1 2015
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Guerrini, M. M., Okamoto, K., Komatsu, N., Sawa, S., Danks, L., Penninger, J. M., ... Takayanagi, H. (2015). Inhibition of the TNF Family Cytokine RANKL Prevents Autoimmune Inflammation in the Central Nervous System. Immunity, 43(6), 1174-1185. https://doi.org/10.1016/j.immuni.2015.10.017