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Gaining entry to an uninflamed brain

Nature Immunology volume 10, pages 453–455 (2009)Cite this article

Little is known about how pathogenic T cells gain access to the uninflamed brain in multiple sclerosis and experimental autoimmune encephalomyelitis. A new study reports that interleukin 17–producing T helper cells enter the uninflamed central nervous system through the choroid plexus by a CCR6-CCL20–dependent mechanism.

The blood-brain barrier is a protective barricade that limits the entry of large molecules and cells such as erythrocytes, platelets and lymphoid cells into the central nervous system (CNS) in normal conditions. Although there are well known 'windows' in this barrier, particularly adjacent to the hypothalamus, which allow cytokines such as interleukin 1 (IL-1), IL-6 and tumor necrosis factor to elicit fever1, in general, the brain is very selective about allowing large molecules and cells to gain entry. Yet, how autoreactive T cells gain access to the uninflamed brain to initiate disease has remained unknown. In this issue of Nature Immunology, Reboldi and colleagues2 demonstrate that autoreactive IL-17-producing T helper cells (TH-17 cells) enter the CNS through a 'chink in the armor' of the blood-brain barrier. In a special location called the 'choroid plexus', these TH-17 cells initiate the inflammatory cascade, causing demyelination through an interaction between the chemokine CCL20 and its receptor, CCR6.

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Figure 1: CCR6-dependent entry into the CNS.

Kim Caesar

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Authors and Affiliations

  1. Robert C. Axtell and Lawrence Steinman are in the Department of Neurological Sciences and Neurology, Stanford University, Stanford, California, USA. steinman@stanford.edu,

    Robert C Axtell & Lawrence Steinman

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  1. Robert C Axtell
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Axtell, R., Steinman, L. Gaining entry to an uninflamed brain. Nat Immunol 10, 453–455 (2009). https://doi.org/10.1038/ni0509-453

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