Cell
Volume 148, Issue 3, 3 February 2012, Pages 447-457
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Article
Regional Neural Activation Defines a Gateway for Autoreactive T Cells to Cross the Blood-Brain Barrier

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Summary

Although it is believed that neural activation can affect immune responses, very little is known about the neuroimmune interactions involved, especially the regulators of immune traffic across the blood-brain barrier which occurs in neuroimmune diseases such as multiple sclerosis (MS). Using a mouse model of MS, experimental autoimmune encephalomyelitis, we show that autoreactive T cells access the central nervous system via the fifth lumbar spinal cord. This location is defined by IL-6 amplifier-dependent upregulation of the chemokine CCL20 in associated dorsal blood vessels, which in turn depends on gravity-induced activation of sensory neurons by the soleus muscle in the leg. Impairing soleus muscle contraction by tail suspension is sufficient to reduce localized chemokine expression and block entry of pathogenic T cells at the fifth lumbar cord, suggesting that regional neuroimmune interactions may offer therapeutic targets for a variety of neurological diseases.

Highlights

► A mouse multiple sclerosis model reveals a gateway through which T cells enter the CNS ► T cell entry occurs via dorsal blood vessels that contact a specific region of the spine ► Entry depends on high CCL20 chemokine output from the IL-6 amplifier in dorsal vessels ► Leg soleus muscle activity enhances chemokine expression in dorsal blood vessels

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Present address: Genetrix SL, Plaza de la Encina, 10–11 Tres Cantos, 28760 Madrid, Spain