Graduate School of Frontier Biosciences, Osaka University

Japanese

Regional Neural Activation Defines a Gateway for Autoreactive T Cells to Cross the Blood-Brain Barrier

Journal Cell 148, 447–457 (2012)
Authors Yasunobu Arima (1), Masaya Harada (1), Daisuke Kamimura (1), Jin-Haeng Park (1), Fuminori Kawano (2), Fiona E. Yull (3), Tadafumi Kawamoto (5), Yoichiro Iwakura (6), Ulrich A.K. Betz (7), Gabriel Márquez (8), Timothy S. Blackwell (3, 4), Yoshinobu Ohira (2), Toshio Hirano (9, 10), Masaaki Murakami (1)
  1. Laboratory of Developmental Immunology, JST-CREST, Graduate School of Frontier Biosciences, Graduate School of Medicine, and WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan
  2. Department of Health and Sports Sciences, Graduate School of Medicine, and Graduate School of Frontier Biosciences, Osaka University, Osaka 560-0043, Japan
  3. Department of Cancer Biology, Vanderbilt University, TN 37232, USA
  4. Department of Medicine, Vanderbilt University, TN 37232, USA
  5. Radioisotope Research Institute, Department of Dental Medicine, Tsurumi University, Yokohama 230-8501, Japan
  6. Center for Experimental Medicine and Systems Biology, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
  7. Merck KGaA, Portfolio Development Merck Serono, 64293 Darmstadt, Germany
  8. National Center for Biotechnology (CNB-CSIC), Darwin 3, 28049 Madrid, Spain
  9. Osaka University, Osaka 565-0871, Japan
  10. Laboratory of Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, Japan

Contact:
Masaaki Murakami
murakami@molonc.med.osaka-u.ac.jp
Laboratory of Developmental Immunology, JST-CREST,
Graduate School of Frontier Biosciences, Graduate School of Medicine, and Immunology Frontier Research Center, Osaka University
Title Regional Neural Activation Defines a Gateway for Autoreactive T Cells to Cross the Blood-Brain Barrier
PubMed 22304915
Abstract Although it is believed that neural activations can affect immune responses, very little is known about the neuro-immune interactions involved, especially the key regulators for immune signals to reach from the blood to the CNS. We here describe dorsal blood vessels in the 5th lumbar-cord that show excess chemokine levels in a manner dependent on regional neural activations of the soleus-muscle. These responses appear to act as a gate for blood cell populations including immune cells to enter the CNS. This gate can promote pathogenic T cells inflammatory inflow, which risks autoimmune diseases like multiple sclerosis. Therefore, these regional neuro-immune interactions may offer new therapeutic targets for neurological diseases.
Description Research highlights are;
(1) A mouse multiple sclerosis model reveals a gateway through which T-cells enter the CNS, (2) T-cell entry occurs via dorsal blood vessels that contact a specific region of the spine, (3) Entry depends on high CCL20 chemokine output from the IL-6 amplifier in dorsal vessels, and (4) Leg soleus muscle activity enhances chemokine expression in dorsal blood vessels


Schematic figure of neural activation-induced pathogenic T cell accumulation in the CNS. Neural activation-mediated IL-6 amplifier enhancement in endothelial cells of dorsal blood vessels in the 5th lumbar cord induces CCL20 followed by the accumulation of pathogenic Th17 cells, a critical event for the development of EAE.