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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 publication

DOI

10.1016/j.immuni.2015.10.017

Type

Journal article

Journal

Immunity

Publication Date

08/12/2015

Volume

43

Pages

1174 - 1185

Addresses

Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan; Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO) Program, Takayanagi Osteonetwork Project, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan.

Keywords

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